2020 Liver Cancer News
Black Patients with HCC Have Worse Overall Survival
A team of investigators published findings stating, “Disparities in HCC incidence have been consistently documented over the past three decades, with non-Hispanic Black, Hispanic and Asian populations having higher age-adjusted incidence rates compared to non-Hispanic whites.” The team reviewed 35 medical studies including over 563,000 patients. They found that of all the groups of people, black patients had the worse overall survival time. While Hispanic and Asian patients had better survival compared with white patients. Now that the disparities have been identified, researchers must now focus on determining the root causes of disparities in HCC, identify actionable intervention targets, and advocate for system-level change.
The liver is one of the biggest organs in the human body and is responsible for detoxing the body, breaking down carbohydrates and making glucose. The liver also stores the essential nutrients and creates bile, which is necessary to digest and absorb nutrients from food. Certain foods and drinks can promote liver health. Research has shown that blueberries, raspberries and cranberries contain antioxidants called polyphenols, which help protect the liver from getting damaged. Coffee has been shown to protect the liver against fatty liver disease and reduce the risk of chronic liver disease. A study published in 2015 found that green tea can help reduce overall fat content, fight against oxidative stress and reduce the signs of non-alcoholic fatty liver disease. It is also important to include garlic in your regular diet to help stimulate the liver.
Hepatocellular Carcinoma (HCC) is the sixth most common cancer worldwide with risk factors including hepatitis B virus, hepatitis C virus, and excessive alcohol intake. Among the eight major pharmaceutical markets, the Asia-Pacific markets of Japan and urban China have a considerably higher burden of HCC. By the end of 2020, the diagnosed incidence of HCC in urban China is expected to be approximately 25 cases per 100,000 population, and in Japan is expected to be nearly 30 cases per 100,000 population. This makes urban China and Japan up to two times higher than the remaining markets and represents over 70% of total new HCC cases occurring in the 8 major pharmaceutical markets. To help alleviate the burden of HCC in Japan and urban China, future prevention efforts and strategies should be aimed at lowering the prevalence of major HCC risk factors.
Gene Biomarkers Indicate Liver Toxicity Quickly and Accurately
A research team at the University of Illinois has developed a gene biomarker identification technique that significantly decreased the time required for testing new biopharmaceutical products and maintaining a high level of accuracy. Product testing usually involves lengthy and expensive animal studies. "This research aimed to identify the smallest set of indicators from the liver to predict the toxicity and potential liver cancer," says Zeynep Madak-Erdogan, associate professor in the Department of Food Science and Human Nutrition at U of I and a lead author on the study. The team shows that collaboration between life sciences and computer sciences is very important for this work.
Microbubbles Create Greater Radiation Sensitivity in Liver Tumors
A team of investigators from Thomas Jefferson University showed that adding gas-filled, lipid-shell micro-bubbles to transarterial embolization (TARE), and popping them close to tumors, can make them more susceptible to treatment. TARE is a therapy that involves injecting radioactive glass beads into blood vessels in the liver and is recommended for roughly 15 % - 25% of patients with advanced liver cancer. The study contained two groups of patients; one group received TARE alone, and the other underwent TARE plus ultrasound-triggered destruction of micro-bubbles. Overall, patients who received the combined therapy saw much better results, 93% of tumors in the combination group showed a partial-to-complete response to the therapy while only 50% of the tumors in the TARE group alone saw a response.
Treatment Combo Trigger the Antitumor Immune Response
Radiofrequency ablation (RFA) is a minimally invasive, first-line treatment designed to destroy tumors by delivering a high-frequency alternating current through an active needle-electrode inserted into neoplastic tissue. Unfortunately, RFA monotherapy is not sufficient to control hepatocellular cancer (HCC). To develop a more powerful immune-based therapeutic strategy against HCC, the cancer translational research team consisting of physicians, and basic scientists created an integrative therapy that combined RFA with the chemotherapy drug sunitinib. "These results indicate that the sunitinib and RFA-integrated therapy functions as an effective therapeutic strategy that is superior to each therapy, significantly suppressing tumor growth and extending the lifetime of the treated mice," said co-author Eric Kimchi, MD, MBA, Chief of Division of Surgical Oncology and General Surgery.
Currently, in Taiwan, positive results have been reports from the phase II clinical trial of combination therapy of ALK-1 (GT90001) antibody and PD-1 (Nivolumab or Opdivo) antibody for the second-line therapy of advanced Hepatocellular Carcinoma (HCC). GT90001 is a fully human monoclonal antibody against ALK-1 (Activin Receptor-Like Kinase-1, Activin Receptor-Like Kinase-1). The combination was aimed at patients who were intolerant to first-line therapy with Sorafenib or Lenvatinib. During the single-arm, open-ended and two-stage clinical trial researchers mainly observed the safety, tolerability and anti-tumor activity of the combination therapy. Among the 20 evaluable patients, eight patients were observed partial remission (PR).
A Library of Mice to Look Up The Best Liver Cancer Treatment
A team of researchers from Osaka University has developed a technique to study a library of genes in lab mice instead of one specific gene at a time, to help identify which cancer genes drive specific liver cancers. The researchers first took ten cancer genes that are known to be involved in the pathways leading to HCC and used them to build a DNA library. The team worked with liver cells and were able to identify six proteins whose expression was decreased when the FGF19 gene was turned off. Of the six, they determined that a protein known as ST6GAL1 was the most closely correlated with FGF19 in HCC. They went on to show that FGF19-driven liver cancer is susceptible to lenvatinib treatment. "Our results suggest that FGF19-driven HCC, which generally carries a poor prognosis, may be susceptible to lenvatinib," says Takahiro Kodama, lead author of the study.
Sirnaomics to Initiate Phase I Study of STP705 in Treatment of Primary and Metastatic Liver Cancer
irnaomics has received authorization from the U.S. Food and Drug Administration (FDA) to proceed with a planned Phase I clinical study of its leading drug candidate, STP705, for the treatment of liver cancer. STP705 is a small interfering RNA (siRNA) therapy that utilizes a patented polypeptide nanoparticle (PNP)-enhanced delivery system to inhibit expression of TGF-β1 and COX-2 in targeted tissue and cells. Preclinical animal models have demonstrated its effective anti-tumor activity for treatments of Hepatocellular Carcinoma (HCC). Over expressions of TGF-β1 and COX-2 have been previously identified as playing important regulatory roles in tumorigenesis and TGF-β is overexpressed in metastatic HCC tissues. TGF-β is produced by different liver cells and has been shown to induce tumor cell growth. The prior finding shows the molecular analyses of the effects of administering the combination to inhibit tumor cell growth.
Y-90 Therapy Offers Many Benefits in Treatment of Liver Cancer
Patients who are not eligible for surgery or ablation are offered transarterial therapy, in which treatments are administered directly to the tumor from its blood supply, and systemic therapy, which is a medicine that treats the whole body. Radioembolization is a form of transarterial therapy in which small radioactive particles are administered directly into the blood vessels supplying the liver. Radioembolization is an outpatient treatment performed by an interventional radiologist. Radioactive particles containing yttrium-90, also referred to as Y-90, radiation less than half an inch into adjacent tissue and limit the amount of liver exposed to radiation. A past researcher has shown that radioembolization is more effective in treating early-stage liver cancer, where smaller volumes of the liver are treated with significantly higher doses of radiation.
Key Capital to Fast-track Breakthrough Liver Cancer Immunotherapy
Key Capital Corp. has received the FDA's Orphan Drug Designation for Immunitor V5 which has demonstrated tremendous success in all clinical studies to date for the treatment of Hepatocellular Carcinoma (HCC). Immunitor studies report that patients taking just one oral Immunitor V5 tablet daily exhibited a 12-month response and survival rate in 90% of cases. V5 is not toxic, has no side effects, and does not cause any cytotoxicity. The research shows that V5 has several clinical benefits, primarily, improved liver function and tumor marker alpha-fetoprotein (AFP) decrease. AFP decrease correlates to tumor regression when levels are returned to normal tumors disappear.
Combination Therapy Might Improve Outcomes in Treatment-Resistant Liver Cancer
Researchers at Massachusetts General Hospital have identified a combination of cancer therapy that is effective against treatment-resistant Hepatocellular Carcinoma (HCC) by inhibiting tumor growth and increasing survival. The treatment combines the multikinase inhibitor drug regorafenib to reprogram the tumor immune microenvironment, and programmed cell death 1 (PD1) antibodies to stimulate anti-tumor immunity, which has shown improved survival in mouse models of HCC. Anti-VEGFR inhibitors work to control growth by normalizing tumor vasculature and increasing T-cell infiltration into tumors. This combination treatment has been shown to nearly double response rates 15% to 20% of HCC patients who typically respond to anti-PD1 treatment alone.
Genetron Health Provides Update on HCCscreen™ for Liver Cancer Early Screening in China
Wuxi municipal government and the National Cancer Center (NCC) in China have collaborated for the public health initiative called “Liver Cancer Early Screening Comprehensive Prevention and Control Project.” Their goal is to increase awareness of liver cancer early screening. Wuxi has selected HCCscreen™ for local residents who are high-risk individuals for extracellular carcinoma (HCC) and has committed to administering 150,000 tests over three years. Genetron Health received the U.S. FDA's Breakthrough Device designation for HCCscreen™. Preliminary study data involving HCCscreen shows 297 patients at one center have demonstrated over 92% sensitivity and 93% specificity, as compared to 67% and 99%, respectively in the ultrasound plus alpha-fetoprotein (AFP) arm. HCCscreen also achieved a 35% positive predictive value and 99.6% negative predictive value. In another study, 10 patients had tumor sizes of less than 5 centimeters, seven of which had tumor sizes of less than 3 centimeters, and HCCscreen™ successfully detected all of them, proving its ability in detecting early-stage HCC.
Atezolizumab/Bevacizumab Lays the Groundwork for Optimal Sequencing in HCC
As the combination of atezolizumab (Tecentriq) and bevacizumab (Avastin) is a great advancement for patients with advanced Hepatocellular Carcinoma (HCC), sequencing and dosing strategies are currently being investigated. “Second-line studies are now being conducted in patients who received first-line immunotherapy agents, where they are being combined with multitargeted TKIs or immune-enhancing drugs,” said Milind Javle, MD, a professor in the Department of Gastrointestinal Medical Oncology, Division of Cancer Medicine, at The University of Texas MD Anderson Cancer Center. Additionally, the combination of durvalumab [Imfinzi] and tremelimumab is being evaluated in the first-line setting in the HIMALAYA study. Currently, only a minority of patients who have a compromised liver function and a limited volume of disease fit in the current transplant criteria.
Genetic Disorder Linked to Increased Risk of Liver Cancer in Men
Investigators have found that men with hemochromatosis, a genetic disorder, are ten times more likely to develop liver cancer. Hemochromatosis is a hereditary disorder marked by the buildup of iron, or iron overload, in the body, and if untreated, can lead to liver, joint, and heart damage. In a study looking at 451,186 participants for a median of 8.9 years showed that 1,294 men had the homozygous pathogenic variant linked to hemochromatosis and either developed primary liver carcinoma or passed away. The results show that the risk of primary hepatic malignancy was 7.2% for homozygous men compared with 0.6% for men in the control group. “We were shocked to find that more than 7% of men with two faulty genes are likely to develop liver cancer by age 75, particularly considering that the UK has the second-highest rate of these faulty genes in the world. Fortunately, most of these cancers could be prevented with early treatment,” said research team leader David Melzer, Ph.D.
Antimicrobial Found in Soaps Worsens Fatty Liver Disease in Mice
A recent study conducted by a team of researchers at the University of California San Diego School of Medicine found that triclosan worsens fatty liver disease in mice fed a high-fat diet. Triclosan is an antimicrobial found in many soaps and other household items. The team found that exposure to triclosan promoted liver tumor formation by interfering with a protein responsible for clearing away foreign chemicals in the body. Based on the study results the team believes that while eating a high-fat diet normally triggers the cells to produce more fibroblast growth factor 21, which helps protects liver cells from damage, the team discovered that triclosan interferes with two molecules, ATF4 and PPARgamma, which cells need to make the protective growth factor. In 2016, the U.S. Food and Drug Administration (FDA) ruled that over-the-counter wash products can no longer contain triclosan.
ORIENT-32 is the first randomized Phase 3 study reporting the efficacy and safety of anti-PD-1 antibody-based combination therapy versus sorafenib as the first-line treatment in patients with advanced unresectable Hepatocellular Carcinoma (HCC). The study included 571 patients. TYVYT® (sintilimab injection) in combination with BYVASDA® (bevacizumab biosimilar injection) showed significantly improved overall survival (OS) progression-free survival (PFS) versus treatment with sorafenib. This combination also demonstrated a 43.1% decreased risk of all-cause mortality, and median PFS was 4.6 months versus 2.8 months with sorafenib. Based on the results of the trial, researchers believe that the combination treatment of TYVYT® plus BYVASDA® could potentially provide a new option for the first-line treatment of patients with advanced HCC.
FDA Grants Fast Track Status to SRF388 for Hepatocellular Carcinoma
The FDA has granted the fast-track designation to SRF388 for the treatment of certain patients with Hepatocellular Carcinoma(HCC). SRF388 is a fully human anti-interleukin-27 antibody. IL-27, an immunosuppressive cytokine, has been found to be elevated among patients with liver cancer. Patients who had previously treated with standard therapies, such as VEGF-targeted agents and PD-L1 blockade will be eligible for SRF388. Enrollment has begun for a phase 1 monotherapy dose-escalation study that will evaluate SRF388 for patients with advanced solid tumors as a monotherapy and in combination with other treatments. SRF388 had been previously granted orphan drug designation by the FDA for the treatment of HCC. The designation allows manufacturers to qualify for various incentives, including tax credits for qualified clinical trials and 7 years of market exclusivity.
Unlocking New Mechanisms Behind Liver Cancer
The Science Award 2020 has been awarded to Dr. Peter Dietrich, from the Department of Medicine 1- Gastroenterology, Pneumology and Endocrinology at UKER for his work to discover a mechanism in which liver cancer cells take a substance formed by benign liver cells and use it for their malignant growth. NPY works on various types of cells via receptors, which are located on the surface of the cell and transmit signals to the interior of the cells. The current study shows that large numbers of these NPY receptors are located on the surface of liver cancer cells. When NPY attaches to the receptors, it activates them, and this can lead to accelerated growth of cancer cells and cause metastasis. In animal models, using specific drugs to inhibit the NPY receptors proved to be an effective way to significantly slow the growth of liver tumors. The growth of malignant cancer cells causes inflammatory substances to be produced which in turn encourages normal liver cells to produce large amounts of NPY.
Liver Cancer Is Rising Fastest in Rural America
The rise in liver cancer incidence has been observed in rural areas according to a recent study. Christina Gainey, MD, of the University of Southern California in Los Angeles, suggested that the disparity between urban and rural incidence levels may be attributable in part to both higher levels of risk factors and poorer access to care. The study included a total of 310,635 cases of HCC, of which 85% were in urban areas and 15% in rural areas. Caucasian people accounted for 57% of urban cases and 82% of rural cases. Blacks and Latinos each accounted for about 16% of urban cases and 8% of rural cases. The overall incidence rate was higher in urban areas with 6.9 cases per 100,000 people, as compared with rural areas with 4.9 cases per 100,000. Although, the average annual percentage increase in new cases was higher in rural areas, with a 5.7% average annual rise, compared with a 3.9% annual rise in urban areas.
Q BioMed's Uttroside-B Receives U.S. Patent in Treatment of Liver Cancer
Q BioMed Inc. has received a Patent titled "Uttroside-B and Derivatives Thereof as Therapeutics for Hepatocellular Carcinoma." The Method Of Use patent covers the use of a new pharmaceutical for the treatment of Hepatocellular Carcinoma (HCC). International and additional U.S. claims are currently under prosecution for the technology which addresses a severe unmet need for a safe and effective drug to treat (HCC). Uttroside-B has shown ten times the potency against HCC as compared to the current standard of care drug in the early pre-clinical investigation. Q BioMed is dedicated to acquiring undervalued biomedical assets in the healthcare sector and providing these target assets, resources, developmental support, and expansion capital needed to ensure they meet their developmental potential and thus enabling them to provide products to patients in need.
Liquid Biopsy Assay Demonstrates High Accuracy for Detection of Hepatocellular Carcinoma
Helio Health, an AI-driven company focused on early cancer detection tests has created the Helio Liver Test. This test is a liquid biopsy assay, which has demonstrated high accuracy and screening value of this cell-free DNA (cfDNA) methylation blood-based assay for the detection of Hepatocellular Carcinoma (HCC). Together with protein markers and demographics, the multi-analyte HCC-specific liquid biopsy was validated in an independent cohort, which included 631 total patients and 291 of whom had HCC. The Helio Liver Test had 88.7% sensitivity in early-stage disease as compared to 57.5% sensitivity with AFP alone.
NICE okays Roche Liver Cancer Immunotherapy, Sanofi’s Rare Disease Drug
Patients with Hepatocellular Carcinoma (HCC) will have an immunotherapy-based treatment option after the National Institute for Health and Care Excellence (NICE) gave the green light to the United Kingdom National Health Service (NHS) to fund Roche’s Tecentriq and Avastin combination therapy. This decision was based on findings of the phase 3 IMbrave 150 study, which showed an improvement in overall survival compared with Bayer’s Nexavar (sorafenib). It is the first treatment to be approved in Europe for over a decade that has improved overall survival for people with previously untreated advanced or unresectable HCC. The disease is also becoming more common, Roche projects a 38% increase in cases.
Enhancing Survival of HCC Patients in The New Era - A Multi-disciplinary Team Approach
Singapore's Health Sciences Authority (HSA) recently approved the combination treatment of Tecentriq + Avastin for patients with inoperable Hepatocellular Carcinoma (HCC). This combination is an immunotherapy regimen, which has been proven to enhance overall survival and progression-free survival, as compared to the current standard of care. “Patients are able to tolerate therapy much better and have fewer adverse events, most of which are manageable giving them a higher quality of life. Hence, I would consider this breakthrough therapy,” stated Prof Lim Seng Gee (NUH) of Singapore's multi-disciplinary team (MDT). He also explains that treatment options are largely dictated by the stage of the disease, for example, a small tumor in a patient with advanced liver disease makes options very limited.
Helio Health has created a cell-free DNA (cfDNA) methylation blood test for the detection of Hepatocellular Carcinoma (HCC) called the Helio Liver Test. This test is a multi-analyte HCC-specific blood test, which provides greater sensitivity and specificity for the detection of early-stage HCC and disease surveillance in high-risk communities. The Helio Liver Test, together with protein markers and demographics, was found effective in an independent cohort of 631 patients. The results showed that the Helio Liver Test produced 88.7% sensitivity in early-stage HCC, while sensitivity for AFP alone was 57.5% while detection with ultrasound, the current standard of care for early-stage HCC detection, has approximately 47% sensitivity. Helio Health is an AI-driven healthcare company focused on commercializing early cancer detection tests from a simple blood draw, with the mission of simplifying cancer screening, detecting cancer at an earlier stage, and saving lives.
Treatment of Liver Cancer with Percutaneous Embolization
Hepatocellular Carcinoma (HCC) accounts for about 90% of all liver cancer cases. Surgical removal of the tumor is the most common method of cancer treatment. The surgery can be very traumatizing to the body as the surgeon also removes part of the healthy tissues that surround the tumor. An alternative treatment is called percutaneous embolization. During chemoembolization, a drug is injected into the hepatic artery which supplies the tumor vessels. As a result of insufficient blood circulation and action of the drug, the tumor’s function and growth are suppressed. The best countries for this type of treatment include Turkey, Germany, and Korea as they are among the top countries in the world in regard to the efficiency of oncology treatment.
Coding and Documentation for Y-90 Radioembolization
Yttrium-90 (Y-90) radioembolization is a current treatment for liver tumors. As this is still a new treatment, it may create unusual challenges for interventional radiologists requiring more comprehensive evaluation and management visits. Documentation of treatment planning, calculation of radiation dosimetry, and placement of radioactive sources are all important factors associated with this treatment. Each Y-90 case presents its own set of circumstances, and a well-constructed operative report will tell the story of the case step by step. Along with careful use, documentation is critical to be properly reimbursed for this procedure.
Unlocking the Potential of Targeted Treatment Options for HCC
Lewis R. Roberts, MBChB, Ph.D., explains that the current challenge for patients with advanced Hepatocellular Carcinoma (HCC) is to identify which are most likely to benefit from frontline treatment regimens. Results of the phase 3 IMbrave150 trial demonstrated that atezolizumab plus bevacizumab led to a 42% reduction in the risk for death compared with sorafenib (Nexavar), as wells as a 41% reduction in the risk of disease progression or death. The combination of nivolumab (Opdivo) and ipilimumab (Yervoy) is approved in the second line, but researchers have also begun exploring nivolumab, a PD-1 inhibitor, as the first-line monotherapy. Although, in the phase 3 CheckMate 459 trial, nivolumab failed to show superiority in overall survival (OS) compared with sorafenib as a first-line treatment for patients with advanced HCC. Roberts said investigators are exploring the role of serum AFP and the role it plays in response to treatment since Ramucirumab (Cyramza) was approved by the FDA, based on the results from the phase 3 REACH2 trial, for patients who have an AFP level greater than or equal to 400 ng/mL and have been previously treated with sorafenib.
Kulik Addresses Transplant and Therapy in HCC
Laura M. Kulik, MD, professor of Medicine, Radiology and Surgery at the Feinberg School of Medicine at Northwestern University discusses the process of diagnosing and treating 77-year-old female patients with Hepatocellular Carcinoma (HCC). The patient presented with risk factors for cholangiocarcinoma with scar tissue, including excessive alcohol use, hepatitis C virus (HCV), and hepatitis B (HBV). Rather than performing a biopsy, Kulik explains that in hepatology doctors prefer to use more noninvasive procedures including the use of Aspartate Aminotransferase (AST) to Platelet Ratio Index score, which looks at the AST and platelet ratio, the size of the spleen, the size of the portal vein, whether there’s presence of varices. Kulik states, “If this patient didn’t have cirrhosis, there’s a potential that this could be another type of a lesion because the risk of HCC is not as high without underlying cirrhosis; about 90% of people with HCC will have advanced fibrosis.”
Prestigious Prize for Study into Liver Cancer Diagnosis and Treatment
Professors Helen Reeves and Fiona Oakley, from Newcastle University’s Faculty of Medical Sciences have been awarded the annual £1m Newton Prize for their continued research which aims to better understand liver cancer by identifying new diagnostic and prognostic biomarkers in the blood to halt the progression of the disease. A team led by Dr Marco Zaki, from Minia University, Egypt, has won the Egypt Country Prize category and up to £200,000 to advance their important work on a project, which could improve the life expectancy of more than half of liver cancer patients.
October Liver Cancer Awareness Month, together we are stronger! (Guest blog)
October is Liver Cancer Awareness Month. Hepatocellular Carcinoma (HCC) is considered one of the leading causes of cancer-related deaths worldwide and is also associated with many liver diseases such as Hepatitis B and C, excessive alcohol intake, Non-Alcoholic Steatohepatitis (NASH), and Non- Alcoholic Fatty Liver Disease (NAFLD). October is the time that the European Liver Patients’ Association (ELPA) focuses on awareness, information, and essential data regarding HCC. In addition, ELPA launched a website entirely dedicated to liver cancer and organized a DiCE Masterclass Series Webinar entirely dedicated to HCC.
Patients with HCC Positively Respond to Opdivo with Yervoy When Nexavar Was Not an Option
In a recent study, a team researched the treatment combination of Opdivo (nivolumab) with Yervoy (ipilimumab) in patients with advanced Hepatocellular Carcinoma (HCC) previously treated with Nexavar (sorafenib). This phase 1/2 randomized clinical trial included 148 patients from 31 centers in 10 countries or territories in Europe, Asia and North America. Patients were randomly assigned to one of three-arm which included varying amounts of Opdivo with Yervoy. The primary endpoints of this trial included tolerability, safety and objective response rate (ORR). Tumors were assessed every 6 weeks until 48 weeks by CT or MR. “Based on the results of this study, nivolumab (Opdivo) 1 mg/kg plus ipilimumab (Yervoy) 3 mg/kg every three weeks followed by nivolumab 240 mg every 2 weeks or 480 mg every four weeks received accelerated approval in the United States as a second-line therapy for HCC,” the study authors wrote. The highest ORR of 32% was recorded for arm A which prescribed patients 1 mg/kg of Opdivo with 3 mg/kg of Yervoy every three weeks at four doses total.
Atezolizumab/Bevacizumab Approved in Europe for Advanced or Unresectable HCC
The European Commission has approved the combination of atezolizumab (Tecentriq) plus bevacizumab (Avastin) for patients with advanced or unresectable Hepatocellular Carcinoma (HCC).The decision was based on findings from the phase 3 IMbrave150 trial, which showed a 42% reduction in the risk of death with atezolizumab/bevacizumab versus sorafenib (Nexavar). This combination is now approved for use in a total of 59 countries. “[Atezolizumab] in combination with [bevacizumab] is the first treatment to be approved in over a decade that has improved overall survival (OS) for people with previously untreated advanced or unresectable HCC,” Levi Garraway, MD, Ph.D., chief medical officer and head of Global Product Development at Roche, stated in a press release.
Exploring Current Treatment Options for Patients With HCC
Ghassan K. Abou-Alfa, MD, a medical oncologist at Memorial Sloan Kettering Cancer Center, discusses the different treatment options currently available for patients with Hepatocellular Carcinoma (HCC). Sorafenib (Nexavar) and lenvatinib (Lenvima), which are both effective tyrosine kinase inhibitors, are available as first-line treatment options. The combination of atezolizumab (Tecentriq) plus bevacizumab (Avastin) is a new first-line treatment available. In the second-line setting, regorafenib (Stivarga) with a condition of prior sorafenib exposure is available, as well as cabozantinib (Cabometyx) in second and third line. Nivolumab (Opdivo) is available as a single agent or in combination with ipilimumab (Yervoy), and also pembrolizumab (Keytruda) as a single agent. Dr. Abou-Alfa explains that sequencing is important, for each patient may be different.
Dietary Restriction Effective in Reducing the Odds of Developing Liver Cancer From Fatty Liver
Liver cancer, which is caused in part by increased fat accumulation in the liver, has been increasing in several countries. The main cause of fatty liver is overeating and lack of exercise. Fatty liver is often improved through eating less, getting more exercise, and reducing body weight. It is also important to improve the prognosis of non-alcoholic fatty liver disease. A research team led by Fangping Jia of the Shinshu University School of Medicine were able to show that reducing food intake by 30% or eating until you are just 70% full is effective in reducing the likelihood of developing liver cancer from fatty liver. Many previous studies show the connection between obesity, fatty liver and Hepatocellular Carcinoma, although the impact and mechanism of dietary restriction on cancer is still in question.
Hepatocellular Carcinoma: A Rapidly Evolving Treatment Landscape
Dr. Richard Finn from UCLA discusses topics pertaining to the use of systemic therapy in advanced liver cancer, including the latest research in the field and the impact of recent clinical trials on making decisions around treatment selection. Finn stresses the importance of the necessity for patients to be assessed in centers with the latest technology and offers a multidisciplinary group, to optimize outcomes for patients. He explains, “Perhaps the biggest advancement in the field on a diagnostic level comes from the robustly established criteria for definitive diagnosis of HCC.” Many organizations including the American Liver Foundation agree that noninvasive diagnosis with imaging is sufficient and enables doctors to make the diagnosis confidently and establish a plan of care that includes treatment.
No Scalpel Required: Targeting Liver Tumors With Interventional Radiology
Interventional radiology (IR) is a technique used by physicians to treat liver cancer. This technique involves imaging guidance, such as CT scans, ultrasound, PET, and MRI that are paired with tools, including needles and catheters, to pinpoint the exact area where treatment is needed. At Memorial Sloan Kettering (MSK), interventional radiologists annually perform over 500 procedures to treat liver cancer. The most commonly used IR approach for liver tumors at MSK is embolization which involves injecting microscopic beads into the blood vessels that feed the liver tumors. The other main IR approach for liver tumors is ablation, by placing a specialized needle into the tumor and destroying it. Doctors can use different techniques to destroy the tumor, including, freezing it (cryoablation) or using radio waves (radiofrequency ablation) or microwaves (microwave ablation) to superheat the tumor. IR specialists also can destroy tumors by directly injecting cancer-killing chemicals, such as pure alcohol (ethanol) or acid.
Korea 1st In World Proving Proton Beam Radiotherapy’s Efficacy In HCC
Based on the results from a prospective, randomized, controlled, investigator-initiated, and phase-3 study, the research trio at National Cancer Center including Professor Park Joong-won of the Center for Liver and Pancreatobiliary Cancer, Professor Kim Tae-Hyun of the Center for Proton Therapy, and Professor Koh Young-hwan of the Department of Radiology, they have identified the effect of proton beam radiotherapy (PBT). Their research shows the safety and efficacy of PBT in patients with Hepatocellular Carcinoma (HCC). The research team randomly assigned 144 HCC patients to two groups, 72 patients to the PBT group, and 72 patients to the radiofrequency ablation (RFA) group. The results showed that the two-year local progression-free survival (LPFS) rate was 94.8& in the PBT arm, versus 83.9% in the RFA arm.
Liver Cancer Diagnoses And Deaths Impacted By Geography And Household Income
Robert J. Wong, MD, MS, of the Veterans Affairs Palo Alto Health Care System, his colleagues, and a team from the Stanford University School of Medicine, analyzed the most recently updated Surveillance, Epidemiology and End Results (SEER) cancer database from the National Cancer Institute which includes 35 % of the US population. The team found that compared with patients in large metro areas with a population of more than 1 million people, patients in more rural regions had 10% higher odds of having advanced liver cancer at the time of diagnosis, and 5% higher odds of dying. Dr. Wong states, "Our study highlights the need to focus on understanding the drivers of poor liver cancer outcomes among underserved and vulnerable populations, including those in rural geographic regions or among low-income households so that targeted quality improvement interventions can more specifically address the needs of these populations.”
Lack Of Awareness Will Lead To Surge In Liver Cancer Deaths
Based on a survey by the British Liver Trust, it was found that 47% of the British population sampled would delay making an appointment with their doctor during the pandemic if they had a loss of appetite, nausea or a swollen stomach. These symptoms are all associated with liver cancer. Dr. Abid Suddle, Medical Advisor to the British Liver Trust said, “These findings once again highlight a worrying lack of awareness and common misconceptions about liver cancer. Unless we act now, this will lead to a surge in liver cancer deaths in the future.” Liver cancer has one of the highest mortality rates in the UK, and the number of people dying from primary liver cancer is expected to rise by 58% between 2014 to 2035.
Informing Decisions In Liver Cancer: Use Biology To Better Characterize The Disease
Hepatocellular Carcinoma (HCC) is the fifth-most-common cancer worldwide and has an estimated five-year survival rate of less than 10%. Lead author Jeffrey Morris, Ph.D., explains that “Instead of using the conventional approach to describe a patient’s status—selecting a subset of clinical factors and biomarkers associated with patient survival or other clinical factors—we developed a novel blood biomarker score. The liver sheds numerous proteins and cytokines into the blood, so blood plasma can contain biomarkers that reflect specific biological characteristics of a liver tumor.” The research team from the University of Texas M.D. Anderson Cancer Center have developed HepatoScore. HepatoScore is designed to provide a measure of disease severity based on a biological signature, which is obtained from a patient’s blood sample. The HepatoScore is based on 14 blood biomarkers.
Africa Loses Millions Of Dollars To Aflatoxins
Evidence shows that aflatoxin ingestion is frequent through contaminated food and is one of the major contributing factors in human Hepatocellular Carcinoma (HCC) in China and sub-Saharan Africa. Aflatoxins, a class of toxic compounds that are produced by certain food molds, are a major food safety challenge in the continent of Africa and can manifest at any point along the food chain. To contain the issue and handle the challenge posed by unsafe food, the African Union Commission (AUC) – Partnership for Aflatoxin Control in Africa (PACA) is working in collaboration with CTA, ILRI, FAO and other stakeholders, and have developed African Food Safety Index (AFSI) to constantly review several areas of land and their impacts on food safety.
Researchers Develop New Tool To Improve The Effectiveness Of Liver Cancer Outreach
In honor of Liver Cancer awareness month, Ju-Yeon Lee, an associate professor of marketing in Iowa State University's Ivy College of Business, and colleagues at Notre Dame, Texas A&M, Rice University and University of Texas Southwestern Medical Center, developed a tool to personalize outreach efforts and recommend the most suitable intervention for the patient. Their technique “Outreach with patient navigation” included the patients receiving usual care and screening letter, plus an outreach call and additional reminder call, and working to identify barriers and provide motivational messaging to encourage screening. Lee found that compared to the usual care baseline, outreach efforts increased screening completion rates up to 24%. The research team, led by Yixing Chen at Notre Dame, conducted a randomized field experiment over the course of several months with 1,800 patients.
Why Is Tecentriq + Avastin Potent Primary Therapy For Liver Cancer?
Korea Biomedical Review has met with Chon Hong-Jae, a professor at the Department of Hemato-Oncology at CHA University Bundang Medical Center, to learn the clinical implication of the treatment combination Tecentriq plus Avastin and changes in local HCC treatment strategies. Research has shown that while Sorafenib has been used as the first-line standard treatment for HCC for more than 10 years and extended survival by two to three months, it caused a significant side effect called limb syndrome. Hong-Jae explains that the reason cancer cells can survive, even though they are different from normal cells, is that immune cells do not attack cancer cells. If there is a marker identifying cancer cells then immunotherapies can be sufficiently effective. Avastin, administered in combination with Tecentriq, also plays a role in “removing the transparent cloak.”
Optimized Sequencing Remains A Top Priority In HCC
Gagandeep Brar, MD, assistant professor of medicine within the Division of Hematologic and Medical Oncology at Weill Cornell Medicine, discusses optimal treatment sequencing of multiple regimens in Hepatocellular Carcinoma (HCC). One sequencing strategy would be to use sorafenib in the first-line setting, followed by regorafenib. One option for patients is the combination of atezolizumab and bevacizumab followed by a tyrosine kinase inhibitor (TKI), such as lenvatinib or sorafenib. Other data has shown that lenvatinib followed by sorafenib has some positive results. Brar explains his recommendation that if a patient were on a frontline TKI, then he would use the combination of nivolumab [Opdivo] and ipilimumab [Yervoy] in the second-line treatment.
Oncotarget: Characterization Of Porcine Hepatocellular Carcinoma For Liver Cancer
The Oncopig Cancer Model is a transgenic pig model that develops site and cell-specific tumors following the recombinase induced expression of heterozygous KRASG12D and TP53R167H transgenes. The ability of Oncopig HCC cells to consistently produce tumors in vivo was confirmed via subcutaneous injection into immunodeficient mice and Oncopigs. Oncopig and human HCC cell lines displayed similar cell cycle lengths, alpha-fetoprotein production, and drug-metabolizing enzyme expression. The rabbit VX2 model has been considered the most relevant and widely used model to test HCC Loco-regional therapies (LRT) to date which shows that there is a crucial need for more clinically relevant large animal models that accurately duplicate human HCC to address unmet clinical needs and clinical practice. The Schachtschneider Research Team concluded that the Oncopig can be utilized to conduct correlative studies for more efficient and consistent investigation of new therapies.
First-In-Human T-Cell Therapy Warrants Further Investigation In HCC
Bruno Sangro, MD, director of the Liver Unit at Clínica Universidad de Navarra and a professor of medicine at the Clínica Universidad de Navarra School of Medicine in Pamplona, Spain, discusses the findings from the phase 1 trial of ADP-A2AFP. ADP-A2AFP SPEAR T-cell is a treatment for patients with Hepatocellular Carcinoma (HCC) which targets alpha-fetoprotein (AFP). SPEAR T cells are engineered T-cell receptor cells, specifically, these cells are engineered so that they can target AFP in this case, presented in an A2A molecule of a tumor cell. The preliminary results of the study show one complete response (CR) with sustained serum AFP reduction among 4 patients treated with the 5 billion or more cell dose of autologous, genetically modified cells. Among the 4 patients treated with the highest dose of cells, 1 patient had stable disease and 2 patients had progressive disease.
FDA Approves New Treatment Regime For Advanced Liver Cancer
Based on the results of the phase 3 IMbrave-150 study, the Food and Drug Administration (FDA) has approved a new first-line treatment for Hepatocellular Carcinoma (HCC). The treatment is a combination of atezolizumab with bevacizumab. Atezolizumab is an immune checkpoint inhibitor and bevacizumab is an antibody against vascular endothelial growth factor (VEGF). “From a clinical rationale, combining these two inhibitors makes sense. Inhibition of either pathway alone has shown activity in Hepatocellular Carcinoma,” explains Bassam Estfan, MD, a gastrointestinal oncologist at Cleveland Clinic. “Attacking both pathways at the same time has shown improved responses and life expectancy rates.” The Phase 3 IMbrave-150 study included 336 patients and reported a 42% reduction in the risk of death with the combination treatment compared with sorafenib.
COVID-19 Pandemic Delays Treatment For HCC, Says French Cancer Center Analysis
According to the results of a study of 6 academic referral centers in Paris, France, there has been an observed decrease in planned treatment and significant delays of treatment in patients with advanced Hepatocellular Carcinoma (HCC) due to the coronavirus disease 2019 (COVID-19) pandemic. Giuliana Amaddeo, MD, Ph.D. and colleagues performed a retrospective analysis to determine the impact of the pandemic on the management of patients affected by HCC in the metropolitan area of Paris. The team reported that the rate of treatment was 56.7% in the 2019 group, versus 43.7% in the group treated in 2020. The main reasons for the delay in treatment in the 2020 group were COVID- 19–related issues (77.0%), treatment-related factors (11.4%), delays due to materials (5.0%), and patient factors (6.5%).
Women With Liver Cancer Are More Likely To Have NAFLD Than Men
Meaghan Phipps, MD, of the Columbia University Irving Medical Center, in New York City, and colleagues have recently reported that women with Hepatocellular Carcinoma (HCC) are more likely to have non-alcoholic fatty liver disease (NAFLD) than men. Researchers studied the history of 5,327 adults, with an imaging or biopsy-proven diagnosis of HCC, of whom 1,203 (23%) were women. The team found that NAFLD was more common in women, showing that 23% of them had the condition compared with 12% of men. However, alcoholic liver disease was more common in men, reporting that 15% of men had it, versus 5% of women. The most common cause of liver disease in women was shown to be hepatitis C. The researchers included 5,327 adults with an imaging or biopsy-proven diagnosis of HCC, of whom 1,203 (23%) were women. These participants were diagnosed between January 2000 and June 2014 at five different academic medical centers. Women were older than men at the time of their diagnosis. The cause of their HCC was identified based on imaging and clinical and tissue analyses.
Phase 1 Trial Of ET140203 T-cell Therapy Starts Enrolling Adults With Advanced Liver Cancer
Eureka Therapeutics is conducting a Phase 1/2 trial, called ARYA-1, of its ET140203 T-cell therapy in adults with advanced Hepatocellular Carcinoma (HCC). The study is actively enrolling patients from the City of Hope Medical Center and the University of California Davis. ET140203 contains patient-derived immune T-cells which have been genetically modified to target and destroy cancer cells containing AFP protein complexes, and uses the Artemis cell receptor platform, which is designed to take advantage of T-cells’ natural mechanisms to fight against cancer. According to Eureka, this technology also enables ET140203 modified T-cells to penetrate solid tumors and has been shown to do so in animal models, suggesting their potential efficacy in human patients.
Singapore Identifies Pivotal Fetal-Like Reprogramming Of Tumour Ecosystem
In a comparative study, a team of researchers and clinician-scientists from several health organizations in Singapore, have identified a “fetal-like” reprogramming of the tumor ecosystem in human Hepatocellular Carcinoma (HCC). The researchers mapped approximately 200,000 single cells in the human liver across the timeline from fetal development to terminal liver cancer which led to the discovery of two new fetal-associated cell types in the tumor ecosystem in HCC. The team identified the reappearance of fetal-like endothelial cells, which are responsible for blood supply, and fetal-like macrophages, an immune cell type that serves as the body’s first line of defense against pathogens. The team identified the sequential activation of vascular endothelial growth factor (VEGF) and Notch signaling pathways that led to fetal-like reprogramming of endothelial cells and macrophages are activated during fetal-liver growth, and switched off thereafter, but are re-activated during the development of liver cancer.
According to a phase 3 study conducted in China which included 315 patients, it was found that patients with Hepatocellular Carcinoma (HCC), whose tumors couldn’t be surgically removed, lived longer after being treated with hepatic arterial infusion chemotherapy (HAIC) compared with those who received transarterial chemoembolization (TACE). During the trial, patients who were treated with HAIC received up to six cycles, whereas TACE was given on demand. The researchers found that overall survival (OS) was 23.1 months with HAIC versus 16.07 months with TACE. HAIC patients also had a higher overall response rate compared with TACE patients, 45.9% versus 17.9%, respectively. Median progression-free survival (PFS) was 9.63 months in the HAIC group, versus 5.4 months in the TACE group. Although, HAIC had a better safety profile compared with TACE.
$50K Grant Supports Exploration Of Treatment For Liver Cancer
Rutgers Cancer Institute is New Jersey’s only National Cancer Institute-designated Comprehensive Cancer Center. Recently, Kristen Spencer, DO, MPH, medical oncologist, and researcher X.F. Steven Zheng, Ph.D., has been awarded $50,000.00 towards a project which can help identify a potential treatment for patients with Hepatocellular Carcinoma (HCC). Based on recent research at Rutgers Cancer Institute, it was discovered that too much of the androgen receptor, a protein that binds male hormones called androgens, are present in many HCC tumors and promote HCC cancer cell growth. They also found that another protein, called mTOR, enables too much of the androgen receptor to be present by preventing it from being broken down. In this project, investigators will examine how a drug that blocks mTOR alone, one that blocks the androgen receptor alone, or the combination of both impact growth of both human HCC cancer cell colonies in petri dishes and HCC tumors grown from human HCC cells transplanted into mice.
ILCA Data Reignite Interest In AFP As A Biomarker For HCC
“AFP is the most widely used marker in HCC and is considered reflective of tumor activity and burden,” Andrew Zhu, MD, Ph.D., explains in a presentation at the International Liver Cancer Association (ILCA) 2020 Virtual Conference. AFP ( α-fetoprotein) is a glycoprotein that is produced during fetal stages of development but rapidly declines after birth and typically remains at low levels throughout the remaining life cycle. AFP has long been established as a biomarker for screening and diagnosis of HCC, although its role in treatment selection and prognosis following systemic therapy is a moving target. Research shows that an AFP level greater than 400 ng/mL is a predictive factor for overall survival (OS) in HCC. In the phase 3 REACH trial, while ramucirumab failed to show benefit over placebo in patients with advanced HCC following frontline sorafenib, subgroup analysis of patients with elevated baseline serum AFP levels of 400 ng/mL or greater demonstrated a significant survival benefit with ramucirumab versus the placebo.
SIRT Administered With Nivolumab Demonstrates Positive Safety, Tolerability Results In HCC
Results from the NASIR-HCC (Hepatocellular Carcinoma) phase 2 clinical trial have demonstrated the safety and tolerability of nivolumab (Opdivo) in combination with selective internal radiation therapy (SIRT) containing yttrium-90 resin in patients who were ineligible for transarterial chemoembolization (TACE). After a median follow-up of nearly 16 months, 11% of patients reported a complete response and 26.2% had a partial response. Other results showed that the objective response rate (ORR) in 42 patients was 38.1%, and the disease control rate (DCR) was 81.0. The median overall survival (OS) was 20.69 months, which included a 12-month OS rate of 73.7% and an 18-month OS rate of 61.3%. Senior author Bruno Sangro, MD, Ph.D., director of the Liver Unit at Clínica Universidad de Navarra and a professor of medicine at the Clínica Universidad de Navarra School of Medicine in Pamplona, Spain, explains that patients with intermediate-stage or advanced-stage HCC have limited therapeutic options, but the mainstay of treatment is intra-arterial therapies.
Cancer Immunotherapy ‘Uniquely Suppressed’ By Liver Tumors
A UC San Francisco research team led by Hematology and Oncology Clinical Fellow James Lee, MD, have found that patients who initially respond well to the immunotherapy drugs known as checkpoint inhibitors, such as those that target a protein called PD-1, can develop resistance to these therapies if their cancer has metastasized from its initial location to form additional tumors in the liver. Using special mouse models, the team showed that adding a second type of checkpoint inhibitor in a combination therapy can overcome this resistance and might significantly increase the effectiveness of immunotherapy in patients with liver metastases. “The liver triggers differences in immune cells at distant sites, (and) the liver can choose its enemy – what it wants to protect or not protect,” Lee said.
HCC Treatment Paradigm Evolves Rapidly, Abou-Alfa Says During Liver Cancer Awareness Month
Ghassan K. Abou-Alfa, MD, from the Memorial Sloan Kettering Cancer Center, explains how the treatment landscape of Hepatocellular Carcinoma (HCC) continues to evolve. The current front-line treatment has been the TKI sorafenib (Nexavar), which has been combined with lenvatinib (Lenvima) for a more effective treatment. Second-line treatment options include regorafenib (Stivarga), cabozantinib (Cabometyx), and ramucirumab (Cyramza). Checkpoint inhibitors, such as nivolumab (Opdivo) and pembrolizumab (Keytruda), have also demonstrated promising activity, both as single-agent treatments, as well as in combination with other therapies. Dr. Abou-Alfa discusses the exciting HCC treatment paradigm, which includes the challenges in understanding how to sequence these therapies to optimize outcomes in patients with HCC.
The U.S. Food and Drug Administration (FDA) has granted Breakthrough Device designation to a blood-based next-generation sequencing (NGS) test called HCCscreen(TM), created by Genetron Holdings Limited. This designation is granted for products that have the potential to offer a more effective diagnosis of life-threatening diseases with an unmet medical need, which can help to speed up development to provide patients with quicker access to those devices. HCCscreen(TM) is intended for early detection of Hepatocellular Carcinoma in individuals who are designated to be at high-risk due to chronic HBV infection and/or liver cirrhosis. Currently, HCCscreen(TM) is being tested in its ongoing prospective study with 4,500 individuals. HCCscreen(TM) has thus far achieved a 35% positive predictive value and 99.6% negative predictive value.
Skoltech Scientists Discovered A New Biomarker For Liver Cancer Diagnosis
Results from a recent study found a new panel of potential biomarkers for postoperative diagnosis of various liver cancers. A team of scientists, led by a Skoltech professor Olga Dontsova, discovered a new liver-specific non-coding RNA. Their research found a panel of 4 biomarkers that are differentially expressed in various types of liver cancer and help distinguish between benign and malignant tumors. Tumor markers can help doctors determine whether a patient has cancer. Non-coding RNA is present in all body cells and tissue-specific RNA is found in certain organs and tissues. Another Skoltech team of scientists had previously found undescribed non-coding RNA in the liver that can be used as a biomarker and named the new molecule HELIS (HEalthy LIver Specific) because, unlike classic tumor markers that are indicators of a disease, it operates as a healthy liver biomarker and can even be called an anti-tumor marker.
Phase 3 ORIENT-32 Trial Shows Promise For First-Line Treatment Combo In HCC
The phase 3 ORIENT-32 trial is testing the combination of sintilimab injection (Tyvyt) in combination with bevacizumab biosimilar injection (Byvasda or IBI305) as a first-line treatment for patients with advanced Hepatocellular Carcinoma (HCC) to measure progression-free survival (PFS) and overall survival (OS). The researchers will compare the results to treatment with sorafenib. This study is being conducted in China. Based on the interim analysis conducted by the Independent Data Monitoring Committee (IDMC), the combination has demonstrated a statistically significant improvement in PFS and OS compared with sorafenib. "In China, HCC is the fourth most common malignancy with the second-highest mortality rate. More than half of new and fatal cases of HCC in the world occur in China every year,” explained the principle investigator of the study, Fan Jia, Ph.D., from the Zhongshan Hospital of Fudan University.
Stivarga More Potent In Improving Asian Patients’ Survival
Professor Lim Ho-Yeong of the Department of Hematology and Oncology at the Samsung Medical Center presented results of the REFINE study, a prospective real-world trial on Stivarga which showed that Bayer’s Stivarga ( regorafenib) had a 54 percent improvement in survival extension in real-world data of Asian patients, compared to the survival improvement shown in the previous clinical trial. The REFINE trial is an observational study that prospectively analyzed the effects of Stivarga as a secondary or higher treatment in 500 patients with unresectable HCC. The study results showed that the median overall survival (OS) of 182 patients was 16.3 months, a 52 percent increase compared to 10.6 months shown in the phase-3 RESORCE study, Lim said. The median OS was also longer than 13.2 months.
Singapore Scientists Discover Human Liver Cancer Cells Masquerading As Fetal-Like Cells
A team of researchers from A*STAR’s Genome Institute of Singapore (GIS), Singapore Immunology Network (SIgN), National Cancer Centre Singapore (NCCS), and KK Women’s and Children’s Hospital (KKH), collaborated to identify “fetal-like” reprogramming of the tumor ecosystem in human Hepatocellular Carcinoma (HCC). Previous studies have shown the similarities between embryonic development and tumors, specifically in the expression of fetal-like antigens in cancers. Alpha-fetoprotein (AFP) is one of the key oncofetal proteins found to be elevated in more than 80% of HCC. The researchers discovered that during the development of the fetal liver, which is a process that shares many characteristics typically associated with cancer growth, these fetal endothelial and macrophages help in organ growth and protect the tissue against the body’s immune system.
Post-HCV Treatment Liver Stiffness Linked With Adverse Outcomes
According to a recent study, higher fibroscan liver stiffness after hepatitis C antiviral treatment was associated with the development of decompensated cirrhosis. The team of researchers analyzed data collected from United States veterans who initiated HCV treatment and had at least one liver stiffness before or after therapy. The team assessed whether that liver stiffness impacted the development of decompensated cirrhosis, Hepatocellular Carcinoma (HCC), or death. They concluded that there were no associations between pre-treatment liver stiffness and any adverse outcome. “In patients with HCV treated with anti-viral therapies, obtaining a post-treatment liver stiffness measurement may be beneficial in identifying patients at risk for long-term adverse outcomes,” George N. Iaonnou, MD, MS, of Veterans Affairs Puget Sound Healthcare System and colleagues wrote.
Chinese, Pakistani Companies To Jointly Set Up Cancer Precision Medical Laboratory
Beijing Anlong Gene Medicine Technology Co., Ltd. and Life Rehealth Technology Pakistan Co., Ltd., will jointly establish a cancer precision medical laboratory in which the two companies will jointly carry out exploration and research on cancer medical treatment, and the Chinese company will also share its existing medical technologies with Pakistan. “Health knows no borders,” said Dr. Wei Yujun, general manager of Anlong Gene. “In recent years, China’s development in life sciences has attracted worldwide attention. As Chinese medical professionals, we have the responsibility to let cutting-edge technology benefit more groups. Pakistan is a friendly neighbor of China. Under the Belt and Road Initiative (BRI), we should also respond to policies and strengthen medical cooperation between friendly countries.”
A recent patient study has reported to successfully demonstrate the use of exhaled limonene as a breath biomarker to measure liver function and stage liver disease. The positive results validate Owlstone Medical’s EVOC® probe strategy for the development of breath-based diagnostic and prognostic tests for Nonalcoholic Fatty Liver Disease (NAFLD) and associated Nonalcoholic steatohepatitis (NASH). In the study, exhaled breath from 32 cirrhosis patients and 12 cirrhotic hepatocellular-carcinoma patients were compared with 40 controls. Breath samples were analyzed by Owlstone Medical’s Breath Biopsy platform, from which the results demonstrated that limonene levels are associated with alterations in liver function. Limonene, therefore, holds great promise as a marker of liver metabolic capacity.
Roche's Tecentriq + Avastin Gets Positive Chmp Opinion for HCC
The European Medicines Agency’s (EMA) Committee for Medicinal Products for Human Use (CHMP) has given a positive opinion to the combination of Tecentriq (atezolizumab), and Avastin (bevacizumab) for the treatment of adult patients with advanced or Hepatocellular Carcinoma (HCC). Tecentriq is already approved in the United States and the EU either alone or in combination with targeted therapies. The CHMP recommends the approval of the combination for HCC patients who have not received prior systemic therapy. The recommendation from the CHMP was based on results from the phase III IMbrave150 study, which showed that Tecentriq in combination with Avastin reduced the risk of death by 42% and the risk of disease worsening or death by 41% compared with Nexavar in patients with HCC.
Survival Improved With HAIC Over Standard TACE In Unresectable HCC
A team of researchers found that patients experienced great improvement in overall survival (OS) with the addition of hepatic arterial infusion chemotherapy (HAIC) to oxaliplatin, fluorouracil, and leucovorin (FOLFOX) when compared with transarterial chemoembolization (TACE), as treatment of patients with unresectable Hepatocellular Carcinoma (HCC). The study was a phase 3, multi-center, open-label trial conducted in China, which included 315. TACE is the standard of care for patients with unresectable intermediate-stage HCC, and a previous phase II study demonstrated higher treatment response with HAIC with FOLFOX versus TACE, according to study author Ming Shi, MD, Ph.D., Department of Hepatobiliary Oncology, Cancer Center, Sun Yat-sen University, in Guangzhou, China.
Tecentriq Opens Immune-Based Combo Therapy Era For Liver Cancer
The combination of atezolizumab (Tecentriq) and bevacizumab (Avastin), as a treatment for Hepatocellular Carcinoma (HCC), is the first immune-based combo therapy that beat sorafenib according to the results of the IMbrace150 study. Compared to sorafenib, the combo treatment showed better overall survival (OS) and progression-free survival (PFS). Compared to sorafenib, the combo treatment showed better overall survival (OS) and progression-free survival (PFS). The results of PFS show that 55 percent of the combo group did not have progression at six months, versus 37 percent of the sorafenib group. “The most exemplary treatment option that prompted immune-based combo treatment for the first-line treatment of HCC was the use of Roche’s Tecentriq (atezolizumab), anti-PD-L1 immunotherapy, and Avastin (bevacizumab), a vascular endothelial growth factor (VEGF) inhibitor,” said Yu Su-jong of the Gastroenterology Department of the Liver Cancer Center at the Seoul National University Hospital (SNUH).
Cirrhotic Controls In A Pooled Analysis Of Hepatitis D And Hepatocellular Carcinoma
Due to the lack of research on the link between Hepatitis D Virus (HDV) and Hepatocellular Carcinoma (HCC), a pooled analysis, which combines data from individual studies and analyses them as if derived from a single sample would be necessary. The team reported that coinfection with HDV was significantly associated with increased risk of HCC compared to infection with HBV alone. Cirrhosis and HCC are considered the final stages of HDV-associated liver disease.
Predicting Liver Cancer In People Cured Of Hepatitis C
According to a set of studies, three new methods are using demographic characteristics, liver disease severity and readily available biomarkers to help predict who will develop liver cancer after having successful treatment for hepatitis C virus. chronic hepatitis C can lead to Hepatocellular Carcinoma (HCC), and although people who are cured of hep C are less likely to develop HCC, the risk is not eliminated. The studies included 3,929 people with chronic hepatitis C who were cured with direct-acting antiviral (DAA) treatments. Of the 2,829 patients with cirrhosis, 191 developed liver cancer, while only 15 of the 1,097 people with moderate to advanced fibrosis developed HCC. The researchers identified 11 variables associated with the development of HCC, including male sex, age greater than 64, hepatitis C virus (HCV) genotype 3, prolonged prothrombin time (a measure of blood clotting ability), and alpha-fetoprotein (AFP, a liver cancer biomarker).
Russian Scientists Have Developed An Optical Probe For The Diagnosis Of Liver Cancer
If cancer is suspected in the liver, doctors will perform a percutaneous puncture biopsy, during which tissue samples are taken from the liver using a thick-needle or fine-needle aspiration needle. Scientists have created an optical biopsy method, which is performed using a special probe with a diameter of 1 mm. Doctors fix the probe in a biopsy needle, pass radiation through it, and a signal from the tissue is collected. This allows scientists to combine two existing optical technologies that are used to detect cancer. The first is fluorescence spectroscopy, designed to determine the difference in the glow of healthy and malignant tissues under the influence of laser radiation, and the second, diffuse reflectance spectroscopy, provides data on the absorption and scattering of light in tissues.
Priming With Tremelimumab Leads To Greater Efficacy For Durvalumab Treatment In Advanced HCC
According to a presentation by Robin Kate Kelley, MD, associate professor, University of California, San Francisco, clinical activity was observed in Study 22, with a single priming dose of tremelimumab in combination with monthly durvalumab (Imfinzi) as treatment of patients with Hepatocellular Carcinoma (HCC) in the second line and beyond. The study showed that the combination had the most favorable efficacy, safety, and tolerability across all treatment arms in the study. In part 2A, the initial combination administered 75 mg of tremelimumab for 4 doses with 1500 mg of durvalumab every 4 weeks, but the new dosing schedule assessed in part 2B explored administration at 300 mg of tremelimumab once with the same durvalumab dose.
Ramucirumab Maintains Activity, Tolerability After Non-Sorafenib Frontline Therapy In HCC
Findings from an interim analysis of a REACH-2 expansion cohort was consistent with data from the sorafenib-receiving intention-to-treat (ITT) population of phase 3 REACH-2 study to determine the safety and efficacy of ramucirumab (Cyramza) administered after a frontline, non–sorafenib (Nexavar)-based systemic therapy in Hepatocellular Carcinoma (HCC). The subgroup analysis showed that at a median follow-up of 6.5 months, the median progression-free survival (PFS) was 5.5 months. In previously reported data, at a median follow-up of 7.4 months, the median PFS was 2.8 months in the ITT population treated with ramucirumab versus 2.8 months in those treated with placebo. The primary endpoint of the open-label expansion (OLE) cohort evaluation was safety, with secondary endpoints including PFS, OS, overall response rate (ORR), and time to progression.
Dr. Kim On The Safety Profile Of Atezolizumab/Bevacizumab In HCC
In May of this year, the FDA approved the combination of atezolizumab (Tecentriq) and bevacizumab (Avastin) as a first-line treatment for Hepatocellular Carcinoma (HCC). This approval was based on the findings from the phase 3 IMbrave150 trial, which reported a 42% reduction in the risk of death compared with sorafenib (Nexavar). A quality-of-life (QOL) analysis demonstrated that the combination did not compromise QOL for patients, says Richard D. Kim, MD, a medical oncologist within the Department of Gastrointestinal Oncology at Moffitt Cancer Center and an assistant professor of oncology with the University of South Florida College of Medicine. Fewer than 5% of patients experienced the risk of perforation or variceal bleeding with the combination treatment.
Cabozantinib Showcases Efficacy In Patients With HCC And Child-Pugh B
Researchers conducted a retrospective analysis of data from the CELESTIAL trial which demonstrated the potential role for cabozantinib (Cabometyx) in patients with advanced Hepatocellular Carcinoma (HCC). Anthony B. El-Khoueiry, MD, explains that patients with Child-Pugh B liver cirrhosis are associated with poor prognosis. The CELESTIAL trial reported a median overall survival(OS) in patients treated with cabozantinib to be 10.2 months, versus 8.0 months for patients treated with the placebo, and the median progression-free survival (PFS) was 5.2 months, compared with 1.9 months, respectively. A total of 707 patients with advanced HCC and Child-Pugh A cirrhosis, which is the least severe, and who had received sorafenib (Nexavar) previously, and progressed following treatment. Overall, 10.3% of patients experienced deterioration due to Child-Pugh B cirrhosis in the first 8 weeks of the study.
Real-World Study Confirms Safety Of Regorafenib After Sorafenib In Unresectable HCC
According to the ongoing prospective observational REFINE study regorafenib (Stivarga) demonstrated a tolerable safety profile as treatment of patients with Hepatocellular Carcinoma (HCC) in the real world. Most of the study population had received regorafenib as a second-line treatment with sorafenib (Nexavar) or other lines of therapy. Compared with the RESORCE study, the median overall survival (OS) was longer in patients who received regorafenib in the second-line setting after sorafenib. The median OS was 14.8 months among patients who received regorafenib in the second line after sorafenib. The median OS was 13.2 among those receiving regorafenib in any line, and 13.9 months among those who received regorafenib in any line after sorafenib. The median OS was 8.3 months for those receiving regorafenib in the third or later line.
Chemotherapy Drug More Effective When Combined With Microbubbles
The common treatment of Hepatocellular Carcinoma(HCC) is transarterial chemoembolization (TACE), but doctors find that is it too imprecise to be a local drug delivery method. A team of researchers at Tulane University created a combination treatment called gas embolization, which involves vaporizing tiny droplets of perfluorocarbon, a common organic material composed of carbon and fluorine that is used in pharmaceuticals. Their study tested gas embolization alone and in combination with two common cancer drugs, doxorubicin (DOX) and tirapazamine. Gas embolization stops blood flow to the tumor and proved to be highly effective when used in combination with DOX. This method involves perfluorocarbon liquid to be administered intravenously, which then interacts with DOX that has been administered in the body. DOX binds to the surface of the droplets of liquid, which are small enough to travel through capillaries and do not cause blood vessel blockage until they are vaporized, so treatment can be applied at the specific site of the tumor.
Uptake Of Palliative Care In Liver Cancer Needs Improvement, Report Says
Hepatocellular Carcinoma (HCC) is a cancer with a poor prognosis, increasing incidence, and one that carries a certain amount of stigma. The mortality-to-incidence ratio is 0.89. Early HCC rarely shows signs and leads to late diagnosis, with a 5‐year survival under 20%. A team of researchers found that palliative care is underused and referred too late. The main indications for referral were pain, end of life care, and nausea. For inpatients, the median time to death after consulting with palliative care was 3 days. The team also found that 81% of gastroenterologists believed the misconception that palliative care starts only when active therapy ends.
FDA Rejects Keytruda-Lenvima Combo As First-Line Treatment For Liver Cancer
According to a press release, the FDA will not be approving the combination (pembrolizumab) plus Lenvima (lenvatinib) as a first-line treatment for people with advanced Hepatocellular Carcinoma (HCC). The decision was based on the findings from the Phase 1b KEYNOTE-524/Study 116 designed to assess the safety and effectiveness of the combination in patients with advanced HCC. The FDA determined that there wasn't enough evidence that this combination was meaningfully more effective than other approved treatments. The study found that patients lived a median of 8.6 months without signs of cancer progression, and their median overall survival was 22.6 months.
Immunotherapy Combinations Show Promise For Advanced Liver Cancer
Checkpoint inhibitors are antibodies that help the immune system fight cancer. The three that show promise for patients with Hepatocellular Carcinoma (HCC) are Atezolizumab (Tecentriq), nivolumab (Opdivo) and pembrolizumab (Keytruda). The study including 336 people was conducted to test the efficacy of the combination of atezolizumab and bevacizumab. The research team concluded that atezolizumab plus bevacizumab "should be considered a new standard of care" for people with advanced liver cancer. Another study tested the efficacy of nivolumab plus ipilimumab. Of the 148 patients, the overall response rate was 29% among those who had taken sorafenib for six months or less and 36% among those who had used it longer. The respective median overall survival times were 19.2 and 25.5 months.
Lenvima Plus Keytruda Shows Promise For Advanced Liver Cancer
According to a recent study led by Richard Finn, MD, of the David Geffen School of Medicine at the University of California, Los Angeles, the combination of Lenvima (lenvatinib) and Keytruda (pembrolizumab) showed that 88% of participants either experiencing tumor remission or having stable disease. The study included 100 people with inoperable Hepatocellular Carcinoma (HCC). Lenvima is a multikinase inhibitor that targets VEGF receptors and enzymes that play a role in cancer cell growth and the development of blood vessels that feed tumors. Keytruda is a monoclonal antibody that blocks PD-1, an immune checkpoint on T cells that regulates immune function. The overall response rate (ORR) was 46%, and the median progression-free survival (PFS) time was 9.3 months.
New Data On Emerging Treatments For Liver Cancer Raise Hope For Advanced Disease Patients
New treatment options for patients with advanced Hepatocellular Carcinoma (HCC) are now available. The IMbrave150 study investigated the combination of atezolizumab and bevacizumab versus sorafenib and showed improvements in overall survival (OS) and progression-free survival (PFS) with the combination therapy. The CheckMate 040 trial studied the efficacy and safety of nivolumab in combination with ipilimumab in three different dose combinations. The research showed that among 50 patients previously treated with sorafenib, the overall response rate was 32%, including four patients achieving a complete response, and the median OS was 22.8 months. This combination has been approved by the FDA as a second-line treatment after sorafenib.
“A complete response in a patient with advanced liver cancer, and the anti-tumor activity we have reported in other patients with an acceptable safety profile, to date, further support the continued investigation of ADP-A2AFP,” said Elliot Norry, Adaptimmune’s Chief Medical Officer. The Phase 1 trial of SPEAR T-cells targeting alpha-fetoprotein (AFP) showed one of the total of four patients with a dose of 5 billion or more transduced cells had a complete response. SPEAR® (Specific Peptide Enhanced Affinity Receptor) T-cell treatment platform enables the engineering of T-cells to target and destroy cancer across multiple solid tumors. The goal of Phase 1 clinical trial studies does escalation and will evaluate the safety and anti-tumor activity of ADP-A2AFP in patients with HCC who were intolerant to or refused standard-of-care treatment.
Stivarga, Opdivo Have Similar Survival Outcomes In HCC
According to recent research, Stivarga (regorafenib, Bayer) and Opdivo (nivolumab, Bristol-Meyers Squibb) provided similar outcomes as second-line treatments for patients with Hepatocellular Carcinoma (HCC) who did not show a meaningful response using Retevmo. The team of researchers retrospectively evaluated 223 patients with HCC who were treated with regorafenib and 150 patients who were treated with nivolumab as a second-line treatment after sorafenib failure. The team found that progression-free survival (PFS), time to progression, and overall survival (OS) did not differ between the two groups of patients. “In the non-progressors, nivolumab showed significantly better survival outcomes compared with regorafenib, which is likely due to the durable responses of nivolumab,” stated Won-Mook Choi, of the department of gastroenterology at Asan Medical Center in South Korea.
New Models Help Predict Liver Cancer After Successful Hepatitis C Virus (HCV) Treatment
Independent research teams from France and Egypt have been working on the ability to predict which patients may develop Hepatocellular Carcinoma (HCC) after successful treatment for chronic hepatitis C virus (HCV) infection. Using cohort studies of patients with chronic HCV infection who achieved a sustained virological response (SVR) to direct-acting antiviral (DAA) therapy, the teams set parameters to find those at the lowest and highest risk of developing HCC in the future, which could help to individualize HCC surveillance and detect HCC after HCV is cured as early as possible. Among patients who achieved SVR, the researchers identified two distinct types of patients at an elevated risk of developing HCC: one group with elevated serum parameters, and one group with impaired liver function.
Tips For Apps On Using TACE, TAE For Hepatocellular Carcinoma
Research shows that the incidence of HCC in the United States is expected to continue to rise over the next 15 years. However only 10% - 15% of patients with Hepatocellular Carcinoma (HCC) have curative options at the time of diagnosis, and only 5% survive 5 years. Doctors discuss the difference between TACE vs. TAE treatments. Transarterial chemoembolization (TACE) is the standard of care for the intermediate-stage of disease. Ideal patients are those with single tumors. The goal of TACE is to improve quality of life, prolong survival and downstage the tumor for surgical resection. TACE is performed by accessing the femoral artery and directly injecting a chemotherapeutic agent such as mitomycin, cisplatin and doxorubicin. Transcatheter arterial chemoembolization (TAE) utilizes intravascular delivery of embolic microspheres to cut off the blood sully to the tumor without the delivery of chemotherapeutic agents. Controversies remain regarding TAE because it is not clearly established whether embolization has a comparable survival advantage to that of chemoembolization.
Drinking Two Cups Of Coffee A Day ‘Slashes Risk Of Dying From Liver Cancer By 46%
Recent research, published in the Alimentary Pharmacology & Therapeutics journal, showed that two cups of coffee would reduce a person’s risk of dying from liver cancer by 46%. The team of researchers examined liver cancer-related deaths, finding that there were 1.2 million in 2016. Using data sets relating to coffee drinking, and a model that was able to reveal connections between coffee drinking and reductions in liver cancer, the team found that if every person in the world had consumed two cups of coffee a day in 2016, then there would have been 452,861 fewer deaths from liver cancer. It further concluded that if everyone had been drinking four cups a day, then there would have been 723,287 fewer deaths.
The United States Patent and Trademark Office has granted a patent on the use of Milciclib in combination with tyrosine kinase inhibitors (TKIs) such as Sorafenib (Nexavar®), Regorafenib (Stivarga®) and Lenvatinib (Lenvima®) for the treatment of Hepatocellular Carcinoma (HCC). New combination therapies gain popularity and show promise as patients with HCC often develop resistance towards the monotherapies of existing therapeutics. It is thus an urgent need for combination drug treatment approaches targeting different mechanisms to achieve better clinical outcomes. Currently, the Phase 2a clinical evaluation of Milciclib, a broad-spectrum inhibitor of cyclin-dependent kinases, indicated that the treatment was well-tolerated, and produced positive clinical data in sorafenib-resistant patients of HCC. Another study of Milciclib in combination with Regorafenib, a specific TKI drug, in liver transplant patients with HCC recurrence showed that the combination treatment was safe and produced promising clinical responses in delicate and difficult to treat patients.
Rapid Progress In HCC Paradigm Shifts Standards, Sequencing Strategies
As more advances and options become available for the treatment of patients with Hepatocellular Carcinoma (HCC), Bradley G. Somer, MD, an associate professor in the Department of Hematology and Medical Oncology at the University of Tennessee Health Science Center, explains that sequencing approaches will require careful consideration. Somer states, “HCC is a very complex disease. Many of these patients have underlying illnesses. However, new therapies [have emerged]. There is a new standard of care in the first-line setting based on data from the IMbrave150 trial. However, this also adds layers of complexity in terms of how to manage the next line of treatment.” Somer supports the combination of atezolizumab (Tecentriq) and bevacizumab (Avastin) as an excellent new standard of care.
The Canadian, Health Canada has granted market authorization for Tecentriq (atezolizumab for injection), in combination with bevacizumab, for the first-line treatment of adult patients with Hepatocellular Carcinoma (HCC). This authorization is based on results from the randomized Phase III IMbrave 150 study, which showed that the combination of Tecentriq and bevacizumab reduced the risk of death by 42% and reduced the risk of disease worsening or death by 41% when compared with sorafenib. "I'm pleased that for the first time in over a decade I am able to offer patients a new therapy that data indicates can delay progression and improve overall survival in a more meaningful way for my patients,” stated Dr. Jennifer Knox, Staff Medical Oncologist, Princess Margaret Cancer Centre, Toronto.
Jiangsu Hengrui Gets Korea’s Green Light To Pursue Drug Combo In Phase III HCC Trial
Jiangsu Hengrui Medicine Co. has been granted approval from Korea’s Ministry of Food and Drug Safety (MFDS) to begin a phase III trial for combination therapy of camrelizumab and rivoceranib. The study’s co-primary endpoint will be progression-free survival and overall survival. The randomized, open-label, international, multi-center trial will evaluate the safety and efficacy of the combination therapy vs. sorafenib in advanced or metastatic Hepatocellular Carcinoma (HCC) patients who have not received previous systematic treatment. Camrelizumab is a PD-1 inhibitor, a checkpoint inhibitor that blocks the activity of PD-1 (Programmed cell death protein 1), while rivoceranib is a VEGFR-2 inhibitor, a tyrosine kinase receptor inhibitor that reduces angiogenesis leading to anticancer activity. Jessie Zou, Jiangsu Hengrui’s chief medical officer, states “The combination of a PD-1/L1 antibody with a VEGFR inhibitor delivered a significant synergistic effect on efficacy, as well as safety, when used to treat HCC patients.”
Improved Outcomes With Cabozantinib In HCC Across All Baseline AFP Levels
According to exploratory analysis of the phase 3 CELESTIAL trial, cabozantinib prolonged the survival of patients with previously treated advanced Hepatocellular Carcinoma (HCC), even among patients with high serum alpha-fetoprotein (AFP levels), according to exploratory analysis. The team found that among patients with lower baseline AFP levels, the median overall survival (OS) was 13.9 months with cabozantinib, while the group with higher AFP levels, resulted in a median OS of 8.5 months. Among patients with higher baseline AFP levels, the median progression-free survival (PFS) was 3.9 months. “Our analysis shows improved outcomes with cabozantinib relative to placebo in patients with previously treated HCC across a range of baseline AFP levels,” the authors wrote.
Dr. Kim On The Evolving Treatment Landscape Of Advanced HCC
Richard D. Kim, MD, a medical oncologist within the Department of Gastrointestinal Oncology at Moffitt Cancer Center discusses how the treatment landscape of advanced Hepatocellular Carcinoma (HCC) remained largely unchanged since the approval of sorafenib (Nexavar) in 2007. However, the May 2020 approval of atezolizumab (Tecentriq) in combination with bevacizumab (Avastin) for patients with unresectable or metastatic HCC, based on findings from the IMbrave150 trial in which the combination elicited a 42% reduction in the risk of death compared with sorafenib, transformed the paradigm and introduced a new front-line standard of care, says Kim.
Ablative Therapy For Early HCC Reduces Mortality, Hospitalization Vs Surgery
Constantinos T. Sofocleous, MD, Ph.D., Professor of Radiology, Weill Cornell Medical College, New York and Michael A. Choti, MD, Chief of Surgery, Banner MD Anderson Cancer Center, Gilbert, Arizona discuss the best course of treatment of early Hepatocellular Carcinoma (HCC). Choti argued in favor of surgery while Sofocleous advocated strongly for the use of ablative therapy. Although surgical hepatic resection (HR) has been shown to improve survival and disease-free survival over ablation, surgery has led to more complications and a higher rate of mortality than ablation. Thermal ablation will not impede future opportunities for surgery for disease recurrence in eligible patients.
How To Get More Cancer-Fighting Nanoparticles To Where They Are Needed
Nanotechnology carriers are used to deliver drugs to cancer sites directly, which can help a patient's response to treatment and reduce adverse side effects. Unfortunately, in practice, few injected particles reach the tumor site. However, the University of Toronto Engineering researchers have discovered a dose threshold that greatly increases the delivery of cancer-fighting drugs into a tumor. The researchers discovered that injecting a baseline of 1 trillion nanoparticles in mice, in vivo, was enough to overwhelm the cells so that they couldn't take up particles quick enough to keep up with the increased doses. The result is a 12 percent delivery efficiency to the tumor. "The promise of emerging therapeutics is dependent upon our ability to deliver them to the target site," explains Professor Warren Chan.
Addressing How To Treat Patients With Advanced Hepatocellular Carcinoma
Mehmet Akce, MD, an assistant professor in the Department of Hematology and Medical Oncology at Emory University School of Medicine begins with atezolizumab (Tecentriq) and bevacizumab (Avastin) in combination based on data from the IMbrave150 trial to treat patients with advanced Hepatocellular Carcinoma (HCC) in the first-line setting. As long as patients don’t have any conditions that were not studied in the trial, he feels comfortable using this combination in the frontline setting because it has been shown to be superior to sorafenib (Nexavar). Akce stresses that those with a liver tumor occupying more than 50% of their liver would not be suitable for this treatment.
Singal And Kim Talk Trials And Treatments For HCC
Amit Singal, MD, MS, medical director, Liver Tumor Program Clinical Chief, Hepatology The University of Texas Southwestern Medical Center, and Richard Kim, MD, assistant professor, Oncology University of South Florida College of Medicine Moffitt Cancer Center discuss a case of a Hepatocellular Carcinoma (HCC). Singal explains that because this particular patient has good liver function, good performance status, and limited tumor burden, he would be eligible for curative treatments. Singal points out that there is a high risk of recurrence of about 70% at 5 years. Kim discusses the difference between lenvatinib, which has a more biochemical response and more tumor shrinkage, and sorafenib which is harder to tolerate.
UCLA Researchers Receive $2.97 Million Grant To Develop Test For Early Detection Of Liver Cancer
A team of researchers led by Hsian-Rong “HR” Tseng, professor of molecular and medical pharmacology, and Dr. Vatche Agopian, director of Dumont-UCLA Liver Cancer Center were awarded a $2.97 million grant from the National Cancer Institute to develop a nanotechnology-enabled cancer diagnostic tool to help detect early-stage liver cancer for people who are at risk. The nanotechnology-enabled diagnostic technology, called EV Click Chips, is an effective extracellular vesicle purification system. It uses a multimarker cocktail to recognize, enrich and recover extracellular vesicles secreted from the Hepatocellular Carcinoma (HCC) tumor. This tool can be thought of as a liquid biopsy diagnostic approach, capable of noninvasive detection of early-stage HCC, which are usually undetectable using ultrasonography.
Phase 3 OPTIMA Trial In HCC To Continue To Follow Patients For OS
Although there have been 26 consecutive patient deaths between September 2019 and March 2020 in the OPTIMA trial, Celsion Corporation will continue to follow patients with Hepatocellular Carcinoma (HCC). The phase 3 OPTIMA trial is currently examining ThermoDox® in combination with radiofrequency ablation for overall survival (OS). In the trial, patients were randomized to receive ThermoDox® in combination with standardized radiofrequency ablation, or standardized radiofrequency ablation alone. Overall survival is the primary endpoint of the trial, while the secondary endpoint is progression-free survival (PFS). Previous data from a retrospective analysis of 701 patients with HCC in the HEAT trial of ThermoDox® in combination with radiofrequency ablation showed an average 54% risk improvement in OS.
The Debate Continues: How To Treat Early-Stage HCC
“As other cancers are becoming less common, HCC is actually becoming more common,” explains Thomas Karasic, MD, assistant professor of medicine at the University of Pennsylvania. Currently, only about one-third of HCC cases are found early. For those at risk for developing HCC, screening typically involves ultrasounds of the abdomen every 6 months, sometimes combined with a blood test for alpha-fetoprotein (AFP). Choosing the most appropriate course of treatment for the patient depends on the tumor characteristics. The preferred treatment approach is liver transplant if there are no more than three tumors, or the patient has cirrhosis and cannot safely undergo surgery or ablation. If the tumor is small, less than 3 cm, then ablation is usually done.
Shifting Liver Cancer Cells Away From Migratory State Could Reduce Their Drug Resistance
According to new work from scientists at Fred Hutchinson Cancer Research Center and the University of Washington, whether a liver cancer cell is primed to grow or move affects its ability to resist cancer drugs. “We found new [molecular] players that are important in liver cancer and mediate resistance to therapy,” said Hutch systems biologist Dr. Taran Gujral, who co-led the project with Dr. Shao-En Ong at UW. “We found we can restore their sensitivity [to therapy] with drugs.” Dr. Gujral is an expert in the use of kinase inhibitors, treatments that involve molecules that block kinase activity, to untangle kinases’ roles in cellular processes. Dr. Ong had developed a method to measure protein abundance and activation state, while Dr. Golkowski and Dr. Chan combined their expertise to examine the role of kinases in drug resistance in HCC.
Sirtex Medical has launched SIROS™, an innovative system for the delivery of SIR-Spheres® Y-90 resin microspheres. SIR-Spheres® Y-90 resin microspheres are tiny radioactive 'beads' used in selective internal radiation therapy (SIRT), sometimes referred to as Y-90 radioembolization. The treatment consists of precisely formulated glass microspheres that are infused with high-dose Y-90 and are delivered with targeted accuracy into HCC tumors. SIROS™ offers a visual and versatile option for interventional radiologists to deliver SIR-Spheres® to patients with liver cancer. SIROS™’ design features a peel-and-place tubing set, a proprietary needleless D-Vial specifically designed to suspend SIR-Spheres® into a vortex allowing for a more even distribution, and a locking cover to safely secure the microspheres during delivery.
ISMETT Participates In Groundbreaking Liver Cancer Research
A recent study led by Istituto dei Tumori in Milan with contributions from Dr. Salvatore Gruttadauria at ISMETT involved 74 patients diagnosed with nonmetastatic liver cancer and who had already received different therapies to reduce the size of their tumors. Patients were divided into two groups, those who underwent a liver transplant, and those who continued to be treated with non-surgical therapies. Five years following surgery, the research showed 76.8% of the transplanted patients were free from cancer and relapses, while only 18.3% of those who continued with traditional treatments survived. If traditional therapies, such as chemotherapy and radiation, do not result in sufficient improvements, patients can be put on the list for a liver transplant. “This is an excellent randomized clinical trial showing that cirrhotic patients with advanced Hepatocellular Carcinoma could have their tumors shrunk, allowing for liver transplantation and improved overall survival compared to those who did not have a transplant,” said Dr. David Geller, director of the UPMC Liver Cancer Center in Pittsburgh.
Archbold Offers New Therasphere Cancer Treatment
Archbold Memorial Hospital’s Lewis Hall Singletary Oncology Center is working with Thomasville’s VITA Surgery and VITA Vascular, to offer patients diagnosed with liver cancer new therapy treatment. “Therasphere is internal radiation. We are able to inject the radiation directly into the tumor through a catheter that is placed in an artery that we can access from either the groin or the wrist. There’s no cutting, there’s no incision, and it’s done through a very small pinhole about two millimeters in size.” said Dr. Frederick Johnson, an interventional radiologist at VITA Surgery and VITA Vascular. This treatment is aimed for patients for whom surgery is not possible or patients with multiple tumors in both lobes of the liver who are not transplant candidates.
El-Khoueiry Elucidates Recent Updates In The Rapidly Evolving HCC Treatment Paradigm
“A massive evolution has occurred in the treatment of patients with HCC over the past couple of years. Multiple new agents have received approval, and with these approvals, the landscape continues to shift,” said El-Khoueiry, medical director of the Clinical Investigations Support Office at the University of Southern California Norris Comprehensive Cancer Center. He explains that for a long time sorafenib was the only standard, first-line systemic therapy and has shown improved overall survival (OS) compared with placebo with a median overall survival (OS) of 10 to 11 months. Recently, the REFLECT trial proved the non-inferiority of lenvatinib (Lenvima) compared with sorafenib. He also discussed the strict guidelines for the IMbrave150 trial, which compared the combination of atezolizumab and bevacizumab with sorafenib.
China Launches Study On Liver Cancer In Hepatitis B Patients
A research project, sponsored by the Chinese Foundation for Hepatitis Prevention and Control, aimed at lowering the incidence of liver cancer among patients with hepatitis B was recently launched in China. A team of researchers will observe and study the five-year incidence of liver cancer among 20,000 chronic hepatitis B patients in 99 hospitals across the country. It is estimated that 85 percent of China's liver cancer patients have been infected with the hepatitis B virus. The study aims to optimize the clinical treatment path of hepatitis B antiviral therapy and explore ways of reducing the incidence of liver cancer linked to hepatitis B. "We hope long-term treatment and observation can answer questions that traditional clinical trials cannot, like what's the difference in liver cancer incidence between different therapies," said Zhang Wenhong, a leading expert working on the project.
Committed To Change: Blue Faery's Fight Against Liver Cancer
Andrea Wilson, founder and president of Blue Faery: The Adrienne Wilson Liver Cancer Association, explains how much her life changed when she became the guardian of her younger sister Adrienne and again how her life changed when Adrienne was diagnosed with Hepatocellular Carcinoma (HCC). Tests revealed that Adrienne had gotten hepatitis B and C from their mother during childbirth, which can contribute to the development of HCC. Andrea founded Blue Faery to help prevent, treat and cure primary liver cancer — specifically, HCC — through research, education and advocacy. Blue Faery is currently the only nonprofit organization in the United States solely devoted to fighting primary liver cancer.
FDA Approves Tecentriq Plus Avastin For Liver Cancer
Based on the results of the Phase III IMbrave150 study, the FDA has approved a regimen combining the immune checkpoint inhibitor Tecentriq (atezolizumab) and the targeted therapy Avastin (bevacizumab) for the treatment of Hepatocellular Carcinoma (HCC). The study, which included over 500 patients, showed that the combination reduced the risk of disease progression or death by 41%, prolonged overall survival and improved quality of life compared with the standard-of-care treatment, Nexavar (sorafenib). Tecentriq is a PD-L1 checkpoint inhibitor that restores T-cell activity against cancer, while Avastin is a monoclonal antibody that blocks VEGF, a protein that promotes the proliferation of blood vessels that supply tumors and plays a role in immune suppression. Nexavar is a multikinase inhibitor that blocks the action of several enzymes, including VEGFR, BRAF and RET, involved in cell growth pathways.
Dr. Saurabh Performs Advanced Vascular Interventional Radiology Procedures At JK Medicity
Dr. Saurabh Gupta, an interventional radiologist at JK Medicity Superspeciality Hospital, performed Complex Vascular Interventional Radiology procedures and shared some details for a few of the procedures. Dr. Gupta begins, “One patient was suffering from large 7.5 cm Hepatocellular Carcinoma (HCC) and was given Trans Arterial Chemo-Embolization (TACE) therapy for palliation.” He cut off the blood supply of the tumor by obstructing with embolic particles preloaded with a chemotherapeutic drug, which leads to necrosis of the tumor, and reduces its size considerably. Dr. Gupta has worked as an Assistant Professor in the Department of Radiology at Dayanand Medical College and Hospital, Ludhiana, and has attended an Intensive International Course in Chemoembolization (TACE) at Seoul National University Hospital, South Korea. He specializes in performing minimally invasive procedures with precision under image guidance using ultrasound, CT scan and Cath.
New Study Supports Expanded Indication For Lenvatinib In Advanced HCC
Based on the REFLECT trial, Lenvatinib (Lenvima) offers potential benefits for patients with advanced Hepatocellular Carcinoma (HCC). The excluded portion of the study included 152 patients, 95 of whom received lenvatinib as first-line therapy, and 57 patients received it as second- or later-line systemic therapy. As a first-line treatment, patients had a median progression-free survival (PFS) of 5.2 months, and as a later-line treatment, patients had a median PFS of 4.8 months. Globally, REFLECT was a phase III randomized trial conducted in 20 countries that compared lenvatinib to sorafenib (Nexavar) in first-line treatment of patients with unresectable HCC. Among 954 randomized patients, the median overall survival (OS) for lenvatinib was 13.6 months, and the median OS for sorafenib was 12.3 months which met the authors’ predetermined criteria for noninferiority.
Hepatitis B Surveillance And Treatment In The UCSF Department Of Radiology And Biomedical Imaging
Hepatitis B infection can, over many years, lead to liver damage as well as Hepatocellular Carcinoma (HCC) if left untreated. When people with hepatitis B develop liver tumors, they often have no symptoms. In the UCSF Department of Radiology and Biomedical Imaging, patients with hepatitis B are initially screened for liver tumors using ultrasound, followed by CT and MRI if necessary. The team of researchers has adopted new MRI technology (MR Elastography) in which the liver stiffness can be measured non-invasively, allowing patients to avoid needle biopsies. For patients with hepatitis B who develop liver tumors, scientists in the UCSF Department of Radiology will treat the tumors. Interventional radiologists at UCSF will use small catheters to either cut off the blood flow feeding the liver tumors or to selectively inject chemotherapy into the tumor while sparing much of the rest of the body. Radiologists may also treat tumors by heating them, so the patients avoid surgery.
Expert Explores Second-Line Treatment Options For Hepatocellular Carcinoma
Dr. Tanios S. Bekaii-Saab, leader of the Gastrointestinal Cancer Program at Mayo Clinic Cancer Center, discusses which therapies are best in the second-line setting after patients’ disease has progressed after initial treatment. The basic options for second-line treatment are Stivarga (regorafenib) and Cabometyx (cabozantinib). Dr. Bekaii-Saab explains that if a patient’s alpha-fetoprotein level is 400 ng/mL or more, Cyramza (ramucirumab) is another option, along with Yervoy (ipilimumab) and Opdivo (nivolumab), as well as Keytruda (pembrolizumab). Further, Bekaii-Saab says, “We have had several options in the second line, they all came at the heels of sorafenib (Nexavar). We do not have much data that informs us about what to do following atezolizumab and bevacizumab. So, we have to go with what we have.”
Impact Of Covid-19 On Patients With Hepatocellular Carcinoma
The risk of infection of Covid-19 is high in patients with chronic liver disease (CLD), liver transplant, and cancer due to altered immune function. As a result, Hepatocellular Carcinoma (HCC) patients may be at an increased risk for severe Covid-19 symptoms, and more likely to be admitted to intensive care. the pandemic has resulted in an unforeseen disruption in the management of HCC in all stages. Patients who are at risk of developing HCC, such as those with hepatitis B, hepatitis C, non-alcoholic fatty liver disease (NAFLD) and require close monitoring have seen interruption in screening and diagnosis for HCC. Delays to treatment are also at risk of contributing to progression to incurable cancer. Furthermore, Covid-19 has also caused delays in 16 clinical trials for HCC including the Phase II/III TACE-3 trial investigating the safety and efficacy of nivolumab in combination with TACE for patients with intermediate-stage HCC.
Xin Wei Wang, Ph.D., On New Blood Test Able To Identify Those Likely To Develop HCC
A team of researchers led by Xin Wei Wang, Ph.D., co-leader of the NCI Center for Cancer Research Liver Cancer Program has developed a new blood test that may help identify individuals who are likely to develop Hepatocellular Carcinoma (HCC). The team profiled almost 900 serological samples and used a synthetic virome technology, titled VirScan, to detect the exposure history of these individuals. They developed a unique viral exposure signature (VES) that could discriminate HCC cases from at-risk or healthy volunteers and then validated this signature in a prospective cohort of 173 individuals with chronic liver disease. The test is still in its early stages of development.
Severance Unveils 3-Step Treatment Program To Treat Advanced Liver Cancer
Currently, the standard treatment for advanced liver cancer is a palliative treatment aimed at improving symptoms. Researchers at Severance Hospital said that they could increase the survival rate of patients with advanced liver cancer by conducting radiotherapy and administering anti-cancer drugs simultaneously. To confirm the therapeutic effect of the radiation-hepatic arterial chemotherapy (LD-CCRT), the research team of Professors Kim Beom-Kyung, Kim Do-young and Seong Jinsil at Yonsei Cancer Hospital conducted a clinical trial of 47 patients with advanced liver cancer. The team confirmed that over 53% of patients decreased tumor size by more than 30 percent, and nine patients dropped down to a lower stage of liver cancer allowing liver resection or liver transplantation to cure them completely.
Celsion's Phase III OPTIMA Study of ThermoDox® in combination with radiofrequency ablation (RFA) for the treatment of Hepatocellular Carcinoma (HCC) has enrolled 554 patients at 65 clinical sites in North America, Europe, China and the Asia Pacific. ThermoDox® is lyso-thermosensitive liposomal doxorubicin (LTLD) which delivers high concentrations of doxorubicin to a region targeted with the application of localized heat at 40°C. The Data Monitoring Committee (DMC) has submitted its recommendation to stop this study based on their analysis which found that the pre-specified boundary for stopping the trial for the futility of 0.900 was crossed with an actual value of 0.903. The final decision to cancel the study is left for Celsion.
Liver Organoid Offers New Promise For Transplantation And The Study Of Liver Disease
A team of Biologists and bioengineers at EPFL have designed a new method for growing human mini livers, known as an organoid. Their process is beneficial for the opportunity to create transplantable lab-grown tissues and has the potential to be a major advance in regenerative medicine. The team used bipotent stem cells that occur naturally in the bile ducts connecting the liver to the gallbladder. “Using our method, we can recapitulate the fibrotic microenvironment and test potential treatments to see whether they stop or reverse the course of the disease,” says lead author, Giovanni Sorrentino, a postdoctoral researcher in the Schoonjans lab.
Will Immunotech Biopharm's Technology Help Combat Scourge Of Liver Cancer In China?
Immunotech Biopharm is undergoing Phase 2 testing of 272 liver cancer patients in 14 hospitals in northern China in efforts to combat the recurrence after tumor-removal surgery. After raising $129 million in the company's IPO, Immunotech will fund clinical trials and commercialization of its "EAL" product—the first cellular immunotherapy product in China to start Phase two testing for solid tumors, according to the company's prospectus. EAL is an activated autologous lymphocyte (AAL) therapy. "EAL extracts target blood cells from the patient, activates them outside the body to restore their anti-tumor capabilities and reinfuses them to the body," explained Wang Yu, CEO of Immunotech.
Viral Exposure Signature Predicts Hepatocellular Carcinoma
According to a study by Jinping Liu, Ph.D., of the National Cancer Institute in Bethesda, Maryland, and colleagues, a viral exposure signature can predict Hepatocellular Carcinoma (HCC) risk before clinical diagnosis. The team used a synthetic human virome technology, VirScan, to perform serological profiling of viral infection history in 899 individuals. A viral exposure signature was developed, and the results were confirmed by a cohort with 173 at-risk patients for HCC development. They found that among at-risk individuals in the validation cohort, the viral exposure signature was significantly associated with HCC status. They concluded that the signature was superior to alpha-fetoprotein and identified cancer patients before clinical diagnosis.
Boost For Liver Cancer Patients With New $10.8 Million World-Class Research Centre
Minderoo Foundation, Curtin University, The University of Western Australia, Harry Perkins Institute of Medical Research, the State Government and charitable organizations have provided a new $10.8 million research center. Professor Peter Leedman, Director of the Harry Perkins Institute of Medical Research, and Curtin University’s Associate Professor Nina Tirnitz-Parker will co-lead a large team that will apply the latest techniques to analyze patient tumors and test new treatments. “This new center will establish organoids, miniaturized versions of an organ, from patient tumor samples that will be profiled,” Associate Professor Tirnitz-Parker said. The Western Australian Liver Cancer Collaborative will include more than 50 researchers from UWA and involve Perth’s three main teaching hospitals, as well as interstate and international collaborators.
HEPANOVA Trial Update: Final Patient With HCC Enrolled To Receive Ttfields/Sorafenib
The phase II prospective single-arm pilot trial, HEPANOVA has enrolled its last patient with advanced Hepatocellular Carcinoma (HCC). This study is investigating the combination of Tumor Treating Fields (TTFields) and sorafenib (Nexavar). The first phase included 9 patients with a treatment duration of about 29 months. Pre-clinical studies showed that 150kHz of TTFields reduced HepG2 and Huh7D12 cell counts from 53% to 64%. In another study, TTFields combined with sorafenib led to a significant reduction in the number of HepG2 and Huh-7D12 cells when compared with TTFields alone and sorafenib alone. Another study demonstrated reduced viability, increased cell death and a significant reduction in tumor volume with TTFields at 150kHz plus sorafenib. In this second phase, 25 patients will receive TTFields at 150 kHz with sorafenib 400 mg twice daily.
The Doctor Called The Most Useful Products For Cancer Of The Liver
According to Dr. Arya Krishnan, there are specific foods that will help liver cancer patients better cope with symptoms, support manpower, and increase the chances of recovery. Krishnan recommends eating five or six times a day, small portions about every three hours. She explains that lean proteins strengthen the immune system and accelerate the healing time of damaged cells. This includes chicken, turkey, fish, eggs, low-fat dairy products, and nuts. Whole grains help increase energy levels, such as oats, brown rice, whole grain pasta and bread. The consumption of fruits, berries, especially ones with rich, dark colors, supplies the body with powerful antioxidants, helping it to fight free radicals. Also, healthy fats contained in avocados, nuts, seeds, and olive oi assist with the absorption of the necessary vitamins, minerals, and other nutrients. And finally, is to drink large amounts of water is extremely important when having liver cancer.
The FDA concluded that Merck’s and Eisai’s early data “do not provide evidence that Keytruda in combination with Lenvima represents a meaningful advantage over available therapies for the treatment of unresectable or metastatic [Hepatocellular Carcinoma] with no prior systemic therapy for advanced disease,” the companies said. The FDA had previously granted breakthrough therapy designation for the combination of Keytruda and Lenvima in newly diagnosed liver cancer, based on the results from Keynote-524, a phase 1b study. According to new data, the combination triggered a response in 36% of previously untreated liver cancer patients, lasting for a median of 12.6 months. The two companies will be doing further testing on the Keytruda-Lenvima combo as a first-line liver cancer therapy in phase 3 Leap-002 study, which is already fully enrolled.
CHA Hospital Predicts Liver Cancer Immunotherapy Response Using ADAM9’s Inhibitory Response
A team of researchers, led by Professor Lee Jo-ho, at the CHA Bundang Hospital, have shown that ADAM9 (A Disintegrin and Metalloproteinase 9) can predict the response to treatment early in chemotherapy for liver cancer. ADAM9 is an enzyme that breaks down proteins and disrupts the body's immune system by cutting off MICA (MHC class I-related chain A), the natural killer cell receptors, expressed on the surface of cancer cells. To test the relationship between ADAM9 expression pattern and cancer progression in patients with liver cancer, the team analyzed genomic data of 370 patients and found that ADAM9 expression was higher in liver cancer tissues than in surrounding tissues, and patients with a higher ADAM9 expression level had a lower survival rate. The team concluded that ADAM9 blood levels increased in the pre-hepatic cancer treatment and ADAM9 blood levels were lower to that of the general population for patients who completely cured their symptoms.
Novocure has enrolled the last of the 25 patients into the HEPANOVA trial, a phase 2 trial testing Tumor Treating Fields in combination with sorafenib in patients with advanced liver cancer. The primary endpoint is the overall response rate. “Tumor Treating Fields therapy has demonstrated efficacy in in-vitro and in vivo models of Hepatocellular Carcinoma,” said Asaf Danziger, Novocure’s Chief Executive Officer. Tumor Treating Fields is a cancer therapy that uses electric fields tuned to specific frequencies to disrupt cell division, inhibit tumor growth and potentially cause cancer cells to die. Tumor Treating Fields does not stimulate or heat tissue, and only targets dividing cancer cells of a specific size. In pre-clinical studies, Tumor Treating Fields delivered at 150 kHz reduced both HepG2 cell counts by 53% and Huh-7D12 cell counts by 64%, as well as increased apoptosis reduced tumor volume. The combined treatment of Tumor Treating Fields and sorafenib led to a greater reduction in the number of HepG2 and Huh-7D12 cells as compared to treatment alone.
Novel Protein Drives Cancer Progression
A team of researchers from the Cancer Science Institute of Singapore (CSI Singapore) at the National University of Singapore (NUS) has found a protein that drives the growth of cancers of the liver by altering the genetic code. The protein, death-associated protein 3 (DAP3), represses a process called adenosine-to-inosine (A-to-I) RNA editing, which normally corrects the genetic code to ensure that genes are expressed correctly. By inhibiting RNA editing, DAP3 acts as an oncogene, a gene that can potentially cause cancer. With the team's discovery, the development of new treatments that target DAP3 for cancer treatment may be possible. The team showed that DAP3 could destroy the binding of ADAR2 protein to its target RNAs, thereby inhibiting the A-to-I RNA editing in cancer cells. This suppression is probably how DAP3 can promote cancer development.
8 Silent Signs Of Liver Cancer
Ghassan Abou-Alfa, MD, medical oncologist at Memorial Sloan Kettering Cancer Center discusses signs of liver cancer. The first common symptom is weight loss without effort. Along with weight loss is a loss of appetite and feeling full quickly, which is a result of excess fluid in the abdomen. Bowel movements will be different than normal as well. If eyes or skin are yellow, a person may be jaundice, another symptom of liver cancer. “Certain characteristics may put you at risk for liver cancer. Those with a history of the virus hepatitis C can develop related liver cancer 10 years after their diagnosis,” Dr. Abou-Alfa says. He continues to explain, “The new driver [of liver cancer] is non-alcoholic fatty liver disease.”
The European Commission Has Granted Orphan Medicinal Product Designation In The EU For MIV-818
The European Commission, following the opinion from the European Medicines Agency (EMA), has granted orphan medicinal product designation in the European Union (EU) for MIV-818, developed by Medivir, for the treatment of patients with Hepatocellular Carcinoma (HCC). Orphan Medicinal Product designation provides certain regulatory and financial incentives, including the potential for a 10-year market exclusivity in the EU, for companies to develop and market therapies that treat a life-threatening or chronically debilitating conditions. MIV-818 is an orally administered treatment designed to selectively treat liver cancer cells and to minimize side effects.
Partnership Gets £4.4m Gov Grant For Better Liver Diagnostics
A new collaboration between Perspectum, Manchester and Nottingham Universities, as well as Roche Diagnostics, GE Medical Systems and Jiva will work together to accelerate the development of (artificial intelligence) AI solutions for liver disease diagnostics, to provide earlier and more accurate diagnoses. To begin this work, Perspectum was granted £4.4 million by the UK government research grant (UKRI). It is all too well known that patients with liver disease often have no symptoms in the early stages, and when finally diagnosed in the stages when liver damage is irreversible, and the risk of cancer has increased. Early diagnosis allows patients to be treated when the disease may still reversible and help prevent the progression of liver cancer.
Microbiome-Based Diagnostic Tool Can Detect Liver Fibrosis And Cirrhosis In Stool Samples
A team of researchers from Salk Institute and UC San Diego has created a new microbiome-based diagnostic tool that can quickly and inexpensively identify liver fibrosis and cirrhosis over 90 percent of the time in human patients. Liver cirrhosis can lead to liver cancer. "The microbiome is a dynamic living sensor of small changes in health and disease in the body, and as such, it provides an accurate readout of body health," says Salk Professor Ronald Evans. The team examined over 160 samples and using data from microbiome genetic profiling and metabolites from the stool samples, the researchers discovered a microbiome signature that was associated with a cirrhosis diagnosis with 94 percent accuracy. The microbiome signature can also determine the stage of liver fibrosis.
Atezolizumab/Bevacizumab Shows Comparable Activity In Older Patients With Advanced HCC
According to a subgroup analysis of phase 3 IMbrave150 trial, the combination of atezolizumab (Tecentriq) and bevacizumab (Avastin) demonstrated comparable clinical activity and safety versus sorafenib (Nexavar) in patients with unresectable Hepatocellular Carcinoma (HCC). At the 836-month follow-up, the subgroup of older patients, age 65 or older showed a 42% reduction in the risk of death, and the younger subgroup showed a 41% reduction in the risk of death. The IMbrave150 is the first randomized phase 3 trial in over a decade to demonstrate a statistically significant and clinically meaningful improvement in overall survival (OS) versus sorafenib in previously untreated patients with unresectable HCC. “The results support the use of atezolizumab and bevacizumab as a practice-changing treatment even amongst older adults with unresectable HCC who have not received prior systemic treatment,” Daneng Li, MD, an assistant clinical professor in the Department of Medical Oncology and Therapeutics Research at City of Hope.
Nivolumab Demonstrates Survival and Safety Benefit in Frontline HCC With Longer Follow-Up
According to Bruno Sangro, MD, PhD., the newest findings from the phase 3 CheckMate-459 trial demonstrate that the continued clinical and safety benefit of nivolumab (Opdivo) monotherapy warrants its consideration as a potential front-line standard of care for patients with advanced Hepatocellular Carcinoma (HCC). “In this balance between improved survival rates and better tolerability, this new analysis of the CheckMate-459 study provides support of the clinical benefit of nivolumab versus sorafenib,” said Sangro. “This provides [us with] an understanding [that] a good response to nivolumab makes achieving a prolonged survival a possibility.” The phase 3 CheckMate-459 trial focused on whether nivolumab, a PD-1 inhibitor, was better in overall survival (OS) than sorafenib, which was the standard of care for many years. The study showed that at the 33-month follow-up, the OS with nivolumab was 16.7 months and more than 14 months with sorafenib.
The Center for Drug Evaluation (CDE) of the China National Medical Products Administration (NMPA) has accepted a supplemental new drug application (sNDA) of BeiGene’s anti-PD-1 antibody tislelizumab for the treatment Hepatocellular Carcinoma (HCC). This decision is based on the results from the Phase 2 trial of tislelizumab of 249 patients with previously treated unresectable HCC. Tislelizumab is a humanized IgG4 anti-PD-1 monoclonal antibody specifically designed to minimize binding to FcγR on macrophages, which has been shown to compromise the anti-tumor activity of PD-1 antibodies. BeiGene, Ltd. is a commercial-stage biotechnology company focused on developing and commercializing molecularly targeted and immuno-oncology drugs for the treatment of cancer.
According to a recent study, higher testosterone levels in men with chronic hepatitis B and diabetes have been shown to have an increased incidence of Hepatocellular Carcinoma (HCC). Having diabetes doubles the risk of individuals with hepatitis B virus infection of developing HCC. In the retrospective cohort study of 928 men with chronic hepatitis B virus infection and diabetes, researchers found that 8.9% developed HCC at a median of 10.7 years. Among patients with testosterone levels in the upper third of the group showed a cumulative incidence of HCC at 5, 10, and 15 years was 4.4%, 12.4% and 19.1%, respectively. The team concluded that this demonstrates an association between higher total testosterone levels and a higher risk of HCC in men with chronic hepatitis B virus infection and diabetes, and is shown to be stronger in patients over 50 years old, and those not taking antivirals.
Enzo Biochem, Inc. has received a patent for the Sphingosine Pathway Modulating Compounds for the treatment of Hepatocellular Carcinoma (HCC) using the company’s proprietary compound SK1-I. Elazar Rabbani, Ph.D., CEO of Enzo Biochem, Inc. said, “our internal studies and the work of others have shown that SK1-I can not only inhibit the growth of various types of cancer cells but can also modulate the activity of immune cells.” SK1-I is a small molecule that specifically inhibits Sphingosine kinase 1. Enzo Biochem is a biosciences and diagnostics company exploring life sciences and intellectual property through the development of unique diagnostic platform technologies.
AMU Scientist, LA Prof Identify Protein Forming Cells Causing Tumour In Liver Cancer
Agra: an AMU zoologist, Dr. Hifzur r Siddique, in coordination with Prof. Keigo Machida of the University of Southern Cal. LA, has discovered protein forming cancerous cells in the body causing the growth of tumor in the liver. It is either a result of alcohol consumption or hepatitis infection. Their research could be seen as a potential therapeutic target for the drug design and give a direction to the management strategy for this deadly disease. Siddique and Machida discovered the molecular mechanisms of a cancer-causing protein called TBC1D15. Siddique said, “Cancer stem cells are rare cells found in the tumor which are responsible for cancer initiation recurrence, indication and metastasis. Thus, these cells were considered as a root cause of almost all cancer.”
Dr. Huey On Challenges Faced With Immunotherapy In HCC
Ryan W. Huey, MD, an assistant professor of the Department of Gastrointestinal Medical Oncology at The University of Texas MD Anderson Cancer Center, discusses the challenges faced with immunotherapy in Hepatocellular Carcinoma (HCC). One such challenge in the HCC space, is a lack of tissue, and therefore the opportunity to find predictive biomarkers is less than it would be in other tumor types, explains Huey. Huey concludes that while some biomarkers in other diseases leave oncologists wanting for a bit more, they can help provide a signal for the rationale for immunotherapy, which is something that is not available in HCC.
Dual Checkpoint Regimen Buoys Prospects For Immunotherapy In HCC
There has been a recent approval of nivolumab (Opdivo) in combination with ipilimumab (Yervoy) as dual immunotherapy for patients with Hepatocellular Carcinoma (HCC). Anthony B. El-Khoueiry, MD, was the lead author of the CheckMate 040 study, which led to the approval. Previously, the single-agent pembrolizumab was approved for patients with HCC who had been treated with sorafenib, based on results from the KEYNOTE-224 trial. The current study demonstrated the overall response rate (ORR) was 33%, with 4 complete responses (CRs) and 12 partial responses (PRs). The duration of response with the combination immunotherapy was 4.6 months to more than 30.5 months and 31% of responses lasted at least 24 months, thus showing a benefit to the nivolumab monotherapy.
Median Technologies has conducted a preliminary retrospective study on the evaluation of the risk of recurrence for patients with primary liver cancer, Hepatocellular Carcinoma (HCC), based on a non-invasive biomarker using The iBiopsy. Median’s iBiopsy® proprietary imaging platform allows for the extraction of non-invasive imaging biomarkers, which are the disease “signatures.” This was a two-part study involving 94 patients - first to accurately quantify liver fibrosis on CT images, and second, to correlate the score of fibrosis with the risk of recurrence in post-operative patients with HCC. The iBiopsy imaging biomarker discovery platform integrates advanced technologies in artificial intelligence to produce three-dimensional image results.
Patients With HCC Shoulder Economic Burdens, Have Insufficient Therapeutic Options
A team of researchers led by Abdalla Aly, Ph.D., associate director of U.S. health economics and outcomes research at AstraZeneca, conducted two studies to better understand the toll of Hepatocellular Carcinoma (HCC) on patients living with the disease. First, they looked at rates of work absenteeism among patients living with HCC in the U.S. Considering 554 patients the team found that 78.5% had missed work, 47.7% had been on short-term disability, and 11.8% had been on long-term disability. They also reported that absenteeism among patients resulted in lost time worth $1,424 per patient per month. The team then conducted a review of existing scientific literature to see what it revealed about the economic and humanistic burden of the disease. Total treatment costs for payers and patients combined ranged from $11,913 to $16,947 per month.
Study Demonstrates Feasibility Of Hologram Technology In Liver Tumor Ablation
In a recent study involving 5 patients has shown positive results in the use of augmented reality guidance with electromagnetically tracked tools, and that the technology may help doctors quickly, safely, and accurately deliver targeted liver cancer treatments. The patients were selected for microwave ablation of their liver tumors. The technology provides a three-dimensional holographic view inside a patient's body, allowing interventional radiologists to accurately burn away tumors while avoiding organs and other critical structures. Information is captured into a proprietary augmented reality application, which utilizes Microsoft's HoloLens technology, a virtual reality headset with transparent lenses, to project a segmented hologram of the patient's imaged anatomy directly onto the patient. Post-procedural imaging showed adequate tumor ablation, and none of the patients experienced tumor recurrence at the three-month follow-up.
The Talk: It’s Time To Move From Curative To Palliative Care
Many physicians confess that they do not typically explain the difference between curative and palliative plans with their patients. Some physicians explain that they avoid discussing end of life planning so that the patient doesn’t get a sense of hopelessness. Palliative care aims to optimize the quality of life and avoid suffering in patients with terminal diseases. Curative care refers to the treatment of the disease. Blue Faery: The Adrienne Wilson Liver Cancer Assoc. team discussed Hepatocellular Carcinoma (HCC) care approaches with physicians, nurses, researchers, and patient advocates. Ineffective curative care robs the patient and their family of quality of life that palliative care may have afforded or enhanced. Doctors should make all options clear for their patients, including end-of-life planning and palliative care for the terminal.
Student-FACULTY Research Team Assessing Early Markers AND Dietary Treatment OF Liver Cancer
An early indicator of metastatic Hepatocellular Carcinoma (HCC) is non-alcoholic Fatty Liver Disease (NAFLD). Associate Professor of Chemistry Angela Stoeckman is currently conducting research focused on understanding the dietary influence on markers of metastatic HCC. She explains that while hepatitis B and C are historically a common cause of liver cancer, those instances are decreasing because hepatitis immunizations are becoming more common. However, alcohol- and diet-related conditions are now being linked more strongly to liver cancer. A high-carbohydrate, high-fat diet—that’s especially high in high-fructose corn syrup—has been dubbed the “Western Diet.” NAFLD is a condition that impacts an estimated one in three Americans, and it can progress into HCC, the fastest-growing type of liver cancer globally.
Contrast-Enhanced MRI Shines Light On Liver Cancer Survival
Sébastien Mulé, a radiologist from Henri Mondor University Hospital in Créteil, south-east of Paris, and colleagues have shown that hepatobiliary MR contrast agent uptake can predict survival in patients with Hepatocellular Carcinoma (HCC). The team found that in 32 patients the quantitative analysis of the hepatobiliary phase (HBP) tumor enhancement in gadobenate dimeglumine (Gd-BOPTA)-enhanced MRI accurately identified microvascular invasion (MVI)-positive HCCs. When compared with dual-tracer 18F-FDG and 18F-fluorocholine PET/CT, the contrast-enhanced MRI method performed well for the prediction of tumor aggressiveness and recurrence-free survival (RFS). The team created a lesion-to-liver contrast enhancement ratio (LLCER) and found that an LLCER of -4.72% or less accurately identified patients with poor recurrence-free survival (RFS) after surgical resection.
NIH Scientists Develop Blood Test To Help Improve Liver Cancer Screening
A team of researchers at the National Cancer Institute (NCI), have developed a new test that can help identify people who are likely to develop Hepatocellular Carcinoma (HCC). The test involves a simple blood test to check for the patient’s previous exposure to certain viruses. “Together with existing screening tests, the new test could play an important role in screening people who are at risk for developing HCC. It could help doctors find and treat HCC early. The method is relatively simple and inexpensive, and it only requires a small blood sample,” said the study’s leader, Xin Wei Wang, Ph.D., co-leader of the NCI Center for Cancer Research (CCR) Liver Cancer Program. The team reasoned that certain interactions between viruses and the immune system may raise the risk of developing HCC. People who have risk factors are recommended to get screened for HCC every six months with ultrasound with or without a blood test for alpha-fetoprotein.
Dr. Musher On Immunotherapy Versus TKIs In HCC
Benjamin Leon Musher, MD, associate professor of medicine, hematology and oncology, Baylor College of Medicine, discusses immunotherapy versus TKIs in Hepatocellular Carcinoma (HCC). Tyrosine kinase inhibitors (TKIs) are a type of targeted therapy which are taken orally in the form of pills. Targeted therapy identifies and attacks specific types of cancer cells while causing less damage to normal cells. Immunotherapy is defined as a treatment or prevention of disease that involves the stimulation, enhancement, suppression, or desensitization of the immune system. Patients respond and sometimes tolerate TKIs better than immunotherapy. Immunotherapy may cause problems in patients with compromised liver function.
Genentech Gets FDA Approval For Tecentriq, Avastin Combo For HCC
The US Food and Drug Administration (FDA) has recently approved Tecentriq (atezolizumab) in combination with Avastin (bevacizumab) for the treatment of Hepatocellular Carcinoma (HCC). Tecentriq and Avastin were both developed by Genentech, a subsidiary of Roche. Tecentriq is a monoclonal antibody designed to inhibit the PD-L1 protein expressed on tumor cells and tumor-infiltrating immune cells, while Avastin is a biologic antibody that can specifically bind to the VEGF protein to interfere with the tumor blood supply. The FDA approval was based on the findings of the phase 3 IMbrave150 study. The combination treatment showed an increase in overall survival (OS) by 42%, and progression-free survival (PFS) by 41%, in comparison to sorafenib. According to Genentech, the Tecentriq, Avastin combination is now the first cancer immunotherapy regimen to have been approved by the FDA for the treatment of HCC.
Ilson Explores Treatment Options For Patients With Metastatic HCC
David H. Ilson, MD, Ph.D., medical oncologist, Memorial Sloan Kettering Cancer Center, New York, NY, discusses the treatment options for patients with Hepatocellular Carcinoma (HCC). The first line of treatment is liver resection if the patient’s liver is healthy enough. the REFLECT trial, involving 1000 patients, demonstrated that Lenvatinib was non-inferior to sorafenib in overall survival (OS), but also suggested better progression-free survival (PFS) for lenvatinib, better time to progression, and a higher response rate for lenvatinib over sorafenib. The IMbrave150 trial investigated first-line treatment with atezolizumab [Tecentriq] plus bevacizumab [Avastin], a PD-L1 inhibitor plus bevacizumab versus sorafenib in first-line treatment in 500 patients. The team presented a significant survival benefit for atezolizumab plus bevacizumab versus sorafenib. The 6-month OS rate was 85% for atezolizumab and bevacizumab versus 72% for sorafenib and showed over a 40% reduction in the risk of death. PFS was also improved with a median difference of about 2.5 months.
AZ Nabs A Positive Study For Imfinzi Plus Tremelimumab In Liver Cancer
In a recent study, called Study 22, involving patients with advanced Hepatocellular Carcinoma (HCC), it was found that a single priming dose with AZ’s CTLA4 inhibitor tremelimumab, followed by PD-L1 inhibitor Imfinzi (durvalumab) given every four weeks, performed the best when compared to other treatment regimens. In Study 22, the tremelimumab/Imfinzi regimen achieved a median overall survival (OS) of 18.7 months. Kate Kelley of the University of California San Francisco (UCSF), the lead investigator in Study 22, said the data suggests that ‘priming’ the immune response with a CTLA4 inhibitor at the start of therapy induces a stronger response with Imfinzi. AZ is comparing the tremelimumab/Imfinzi regimen to standard first-line treatment with Bayer’s Nexavar (sorafenib) in the phase 3 HIMALAYA trial.
Updates In Combination Therapies For HCC
Dr. Ghassan Abou Alfa, from Memorial Sloan Kettering Cancer Center in New York City, discussed current treatments for Hepatocellular Carcinoma (HCC). There have been several studies recently – one involving atlizumab, another the REFLECT study using lenvatinib, and the CheckMate 459 study looking at nivolumab. All three studies compared to sorafenib, the competitor. Researchers found that atlizumab performed better than the single-agent lenvatinib, and the single-agent nivolumab. Other therapies are the single-agent durvalumab, single-agent tremelimumab, tremelimumab plus durvalumab, at two different doses and frequencies. The best treatment found was the tremelimumab 300 single dose plus durvalumab regularly.
Single, Priming Dose Of Tremelimumab Plus Durvalumab Active In Second-Line Hepatocellular Carcinoma
According to the findings of Robin Kate Kelley, MD, of the University of California, San Francisco the combination therapy of 300 mg tremelimumab plus durvalumab appeared to provide the best benefit-risk profile for the treatment of patients with Hepatocellular Carcinoma (HCC). The recent study included 332 patients with advanced HCC and randomly assigned them to single-agent durvalumab, single-agent tremelimumab, tremelimumab 300 mg plus durvalumab, or tremelimumab 75 mg plus durvalumab. The median overall survival (OS) was longest for the tremelimumab 300 mg plus durvalumab arm at 18.73 months. Treatment-related serious adverse events occurred highest with the tremelimumab monotherapy.
First-Line Donafenib May Be Superior To Standard Of Care In Advanced Hepatocellular Carcinoma
Feng Bi, MD, PhD and team at the West China Hospital, Sichuan University, found that donafenib, a multikinase inhibitor, may be superior to sorafenib as first-line therapy for advanced Hepatocellular Carcinoma (HCC). The study included 668 patients with unresectable or metastatic HCC, where half received donafenib and the other half received sorafenib. The overall survival (OS) time in the group using donafenib was 12.1 months as compared to 10.3 months in the sorafenib group. The donafenib group also saw a 17% decreased risk of death. The team saw no significant difference in the median progression-free survival (PFS) time, 3.7 months in the donafenib group vs 3.6 months in the sorafenib group. “Donafenib significantly improves OS over sorafenib with favorable safety and tolerability,” the investigators concluded in their study abstract.
FDA Approves Atezolizumab Combo for Unresectable or Metastatic Hepatocellular Carcinoma
Based on findings from the phase 3 IMbrave150 clinical trial, the FDA has approved the combination therapy atezolizumab (Tecentriq) plus bevacizumab (Avastin), as treatment of patients with unresectable or metastatic Hepatocellular Carcinoma (HCC). The study showed the combination reduced the risk of death by 42% as compared with sorafenib (Nexavar) alone. The study involved 336 patients who received the combination, and 165 patients who received only sorafenib. The objective response rate (ORR) was 27% with the combination versus 12% with sorafenib. The median time to response was 2.8 months with the combination vs. 3.3 months with sorafenib.
The First Step Toward Preventing Liver Cancer Is Being Aware Of The Precursors To Its Development
The prevention of liver cancer may be in the hands of patients, and the risk can be reversible through dietary changes and exercise. By losing weight under a doctor's advice, patients may reverse the case of fatty liver they didn’t know they had, and potentially avoid cancer. Patients who are overweight, have symptoms of liver disease, have type 2 diabetes, drink alcohol regularly or have been exposed to hepatitis have a higher risk of liver cancer. When doctors find that a patient’s liver enzymes are elevated, they will follow-up with additional blood tests and imaging. While CT scanning is an option after hepatitis has been ruled out, a new approach is FibroScan, a specialized ultrasound device that vibrates the liver to measure stiffness due to scar tissue.
New Model Shows How Cells That Cause Liver Cancer Are Created
Through several decades of research, doctors found that there is a subset of cells called cancer stem cells (CSCs) that function similarly to normal stem cells and cause cancer cells to form, renew, and proliferate. This means that if a tumor was removed but the CSCs were left alive, the CSCs would cause cancer to grow back. A team from Okayama University, led by Professor Masaharu Seno and Said Mohamed Abdelsabour Afify, has been able to develop CSCs from a type of normal stem cells by merely exposing them to what is believed to be favorable body environmental conditions, without introducing any mutations or foreign genes. "This is the world's first successful establishment of a liver CSC model from normal iPSCs without genetic manipulation," Prof. Seno remarks. Normal induced pluripotent stem cells (iPSC), are a type of stem cell that can regenerate to develop into any type of human tissue, given the right conditions.
Dr. Parikh On The Role Of Radiation In HCC
Radiotherapy is still an evolving field, in which most of the data are retrospective, explains Neehar Parikh, MD, medical director, Multidisciplinary Liver Tumor Clinic, Living Donor Liver Transplantation Program, assistant professor, Michigan Medicine, University of Michigan. Other treatments include stereotactic body radiotherapy (SBRT), chemoembolization, thermal ablation and surgical resection. SBRT administers very high doses of radiation, using several beams of various intensities aimed at different angles to precisely target the tumor and is thought to be safe and effective. Chemoembolization is performed by placing a small catheter from the blood vessel in your groin into the artery that supplies blood to the liver, resulting in a very highly concentrated dose of an anti-tumoral drug to be delivered.
'Senolytic' Therapy Blunts Liver Tumor Progression In Animal Models
According to new research from a team led by Celeste Simon, Ph.D., a professor of Cell and Developmental Biology in the Perelman School of Medicine at the University of Pennsylvania, a treatment called Senotherapy curbs liver tumor progression in animal models. Senotherapy is a treatment that uses small molecule drugs to target "senescent" cells or cells that no longer undergo cell division. Loss of the enzyme FBP1 in human liver cells significantly increases tumor growth and activates the neighboring hepatic "stellate cells," which make up ten percent of the liver mass, causing tissue scarring and subsequent stellate cell senescence, both of which promote tumor growth. Using genetically engineered mouse models, the team eliminated FBP1and found the disease progressed more rapidly into forms of Hepatocellular Carcinoma (HCC).
Cabozantinib May Be A Match For Regorafenib In Second-Line Advanced HCC
A recent study showed that Cabozantinib had a higher median progression-free survival (PFS) when compared with regorafenib as a second-line treatment of patients with advanced Hepatocellular Carcinoma (HCC). The team used results from two trials, the phase III CELESTIAL trial of cabozantinib versus placebo in 331 patients with HCC who received prior treatment with sorafenib, and the phase III RESORCE trial of regorafenib after sorafenib in HCC in 379 patients. The CELESTIAL trial showed the median overall survival (OS) was 10.2 months with cabozantinib versus 8.0 months with the placebo. Results from RESORCE showed higher alpha-fetoprotein (AFP) level response with regorafenib compared with the placebo. The median OS was 12.0 months in patients with an AFP response versus 7.0 months in those who did not achieve an AFP response.
New Drug Combo Could Improve Survival For Patients With Common Liver Cancer
Results from a recent study show that the treatment combination of atezolizumab and bevacizumab improved survival by 42% for patients with Hepatocellular Carcinoma (HCC). The study included more than 500 patients, and at the 12-month check-in, survival rates were 67.2 % with atezolizumab/bevacizumab and 54.6% with sorafenib. "By using these two drugs with different mechanisms of action together, we have increased the number of patients who respond to this treatment and have increased the duration of these responses as compared to the standard treatment, sorafenib," said the study's lead author, Richard S. Finn, MD, a professor of medicine at the David Geffen School of Medicine at UCLA. Atezolizumab is an immunotherapy drug that increases the body's natural defenses, and bevacizumab is an antiangiogenesis drug that suppresses the growth of a tumor's blood vessels.
People Infected With Hepatitis D Are More Prone To Hepatocellular Carcinoma
Of the 5 types of Hepatitis viruses, Hepatitis D, which can only infect people already infected with Hepatitis B, is one of the most dangerous forms of chronic viral hepatitis because of its possible progression to irreversible liver diseases. Based on a retrospective study a team of researchers, led by Francesco Negro, Professor at the Department of Pathology and Immunology of UNIGE Faculty of Medicine and Head of the HUG Viropathology Unit. found that people infected with Hepatitis D have up to three times the risk of developing Hepatocellular Carcinoma (HCC) compared to those infected only with Hepatitis B. There is currently no treatment for Hepatitis D, aside from interferon, an antiviral and an immuno-modulator which shows minimal effectiveness but has deleterious side effects.
Tiziana Life Delighted With Data From Liver Cancer Treatment Trials In Italy
Tiziana Life Sciences has received positive clinical trial data for its liver cancer treatment Milciclib from two clinical trials in The Granda Ospedale Maggiore Policlinico in Milan, Italy. A Phase 2a clinical trial with orally administered Milciclib in sorafenib-resistant Hepatocellular Carcinoma (HCC) patients met the primary endpoint of being well tolerated with manageable toxicities and no recorded drug-related deaths. The study has shown mean AFP levels (a common tumor biomarker) reduced by approximately 20% within one month of treatment. Prof. Angelo Sangiovanni, the principal investigator, said, “The fact that many of the treated patients continued with the treatment, even after completing 6 months duration of the study, is particularly very impressive.”
Personalized Treatment For Subtypes Of HCC Is The Way Of The Future
The use of new genomic technologies, involving the study of the genetic material of an organism, has made it possible for researchers to identify many subtypes of Hepatocellular Carcinoma (HCC). More research is necessary to identify which patients may respond best to certain treatments, such as immunotherapeutic agents and combinations of others. Yujin Hoshida, MD, Ph.D., associate professor of internal medicine, University of Texas Southwestern Medical Center, states “That may be the place to start to link with specific drug therapies because this way of looking at liver cancer may be an efficient way to identify the potential specific drugs for a specific patient rather than chasing one single target at one at a time for each drug.”
New Treatment Extends Lives Of People With Most Common Type Of Liver Cancer
Researchers found that the combination of atezolizumab, an immunotherapy drug that boosts the body's natural defenses, and bevacizumab, an anti-angiogenesis drug that inhibits the growth of tumors' blood vessels, improved overall survival, reduced the risk of death by 42%, and decreased the risk of the disease worsening by 41% in patients with Hepatocellular Carcinoma (HCC). Atezolizumab and bevacizumab are monoclonal antibodies, which means that they are specialized drugs that attach themselves to specific proteins and disable them. The lead author of the study is Dr. Richard S. Finn, a professor of medicine at the David Geffen School of Medicine at UCLA.
Team-Based Approach Essential In HCC Care
Neehar Parikh, MD explains that a multidisciplinary team is critical in the treatment of patients with Hepatocellular Carcinoma (HCC), and has demonstrated a survival advantage as compared with single-provider care. This multidisciplinary group includes hepatologists, interventional radiologists, medical oncologists, diagnostic radiologists, and palliative care physicians. "HCC is a unique malignancy in that multidisciplinary care has been shown to improve outcomes," said Parikh. "Every patient diagnosed with HCC deserves to know whether they are a candidate for transplant, so they can proceed with [their] treatment." Transplant is associated with the best outcome, regardless of which patient populations are observed.
Racial Inequalities Of Liver Cancer Mortality Increase After Introduction Of Hepatitis C Drugs
According to a recent study from Florida Atlantic University's Schmidt College of Medicine and Baylor College of Medicine, racial inequalities of the mortality rate from liver cancer in the United States has steadily increased from 1998-2016 after the introduction of lifesaving drugs for the hepatitis C virus in 1998. Of the 16,770 deaths from liver cancer among black patients, the excess relative to white patients increased from 27.8% to 45.4% during the period from 1998-2016. The mortality rates among black patients over 55 by 1.7% per year from 1997 to 1997 and 4.7% per year from 2000 to 2016. As opposed to the mortality rate for white patients of this age range from 1979 to 1990 increased by 3.5% per year and only 2% per year from 1990-2016.
Fewer Women Receive Liver Transplants Than Men
More than a decade of research shows that women in the United States with cirrhosis are less likely to receive a liver transplant, and more likely to die on the waitlist, than men. Shortly after the new Model for End-Stage Liver Disease (MELD) score system for liver transplantation was adopted in 2002, the transplant community noticed a persistent disadvantage for women who needed access to a liver transplant compared with men, explained Elizabeth Verna, MD, transplant hepatologist and gastroenterologist at New York-Presbyterian/Columbia University Irving Medical Center, in New York City. Verna and the team performed a prospective study of 90,720 registrants with the Organ Procurement and Transplantation Network (OPTN) database found that women were 20% less likely to be transplanted than men, and women had higher mortality than men four years after listing.
Researchers Reveal Why Liver Cancer Patients React Poorly To Immunotherapy
Liver cancer is one of the five most common cancers in Korea. Patients with advanced liver cancer tend to show poor prognosis as they tend to have tolerance against anticancer, radiation, and targeted therapy. The “cancer stem cells” are known as a major problem that resists to various treatments. The research team at Seoul St. Mary's Hospital confirmed that the expression of the carcinoembryonic antigen-related cell adhesion molecule 1 (CEACAM1) on the cell surface, with high expression of epithelial cell adhesion molecule (EpCAM), increased to avoid immune mechanisms caused by tumor killer cells, such as natural killer cells. The CEACAM1 expression in liver cancer stem cells that manifests EpCAM interferes with the tumor killer cells and keep them from working properly, reducing the immunotherapy’s effect to half.
Locoregional Therapies Remain A Key Element Of Care In HCC
Currently, there are many treatments available for patients with Hepatocellular Carcinoma (HCC). Riad Salem, MD, a professor and chief of Vascular Interventional Radiology in the Department of Radiology at Northwestern University Feinberg School of Medicine explains that treatments include surgical resection, transplantation, ablation, stereotactic body radiotherapy (SBRT), and embolization, but that a multidisciplinary team is needed to determine the optimal use of these approaches. Many patients can benefit from a combination of treatments. Salem states, “For some patients, [local therapy] can postpone toxic systemic therapy. By combining [therapy in this manner], we can optimize [the patient’s care] and expose them to all of the agents they would be good candidates for.”
FDA Grants Orphan Drug Designation To First Liver-Targeted Drug For HCC
Medivir's MIV-818 has been granted Orphan Drug Designation by the FDA for the treatment of patients with Hepatocellular Carcinoma (HCC). This US designation follows an Orphan Medicinal Drug Designation in Europe for the same indication. The current phase Ib study will determine the safety and preliminary efficacy of MIV-818 in patients with liver cancer. Medivir states that the drug has the potential to become the first liver-targeted, oral drug available to patients with HCC. In early March, Medivir announced that the first liver cancer patient was dosed with MIV-818 in the study. Thus far, 5 out of 9 patients had stable disease following treatment with MIV-818. Uli Hacksell, Ph.D., CEO at Medivir, stated, "Patients with advanced liver cancer have limited treatment options and the unmet medical need is large."
Evidence Supports Efficacy, Safety Of Sorafenib In Older Hispanic Patients With Advanced HCC
The frequency of Hepatocellular Carcinoma (HCC) has been shown to increase with increasing age across different populations with a peak age of 70 years, and US Hispanic patients have the second-highest rates after the Asian patients. A team of researchers conducted a retrospective analysis of Hispanic patients with HCC and found that there is no significant difference in median overall survival (OS) for older compared with younger patients. The study included statistics from 118 patients with 87 patients younger than 65 and 31 were 65 and older., with each group comprised of more than 70% Hispanic. The team found that the median progression-free survival (PFS) was 4.6 months and the median overall survival (OS) was 10.2 months for the younger group, and for the older group median PFS was 6.2 months and median OS was 13.5 months. Additionally, the median OS was 11.2 months for Hispanic patients vs 8.7 months for non-Hispanic whites.
A New Treatment For Liver Cancer
Dr. Timofei Zatsepin of Skoltech and a team of researchers from MIT have a new treatment option for liver cancer. Using a siRNA approach, with lipid nanoparticle technology developed in the Anderson laboratory of MIT, the scientists targeted proteins that are involved in apoptosis, a regulated program for cell death. The team notes that only recently, multiple kinase-inhibitor regorafenib and two different check-point inhibitors were approved for patients who progress after sorafenib, but this only increased the overall survival (OS) by 3 months. "Once the mechanism is turned off, the cells become more susceptible to dying. This allows for the chemotherapy to be more efficient, killing more cancer cells, and preventing them from dividing. And although our siRNA reaches all liver cells, the cancer cells are more sensitive, because they are dividing rapidly, so they will be more affected by the treatment whereas normal cells survive," explained Dominique Leboeuf, Skoltech Ph.D. These results are the tireless effort of a long-lasting collaboration between Skoltech and MIT, led by professors Konstantin Piatkov, Timofei Zatsepin and Daniel Anderson.
Studies Investigate Multiple Types Of Therapies In HCC
There are currently many therapy and trial options for patients with Hepatocellular Carcinoma (HCC), as explained by Michael R. Charlton, MD, MBBS, professor of Medicine, director of the Center for Liver Diseases, and co-director of the Transplant Institute at the University of Chicago Medicine. He explains that many drugs are used in combinations for higher effectiveness, such as cabozantinib (Cabometyx) being used with the checkpoint inhibitor nivolumab (Opdivo). He mentions the IMbrave150 trial, which investigated bevacizumab (Avastin) and the checkpoint inhibitor atezolizumab (Tecentriq) in combination. Charlton and colleagues agreed that having guidelines that are actively being updated, so they reflect data as they emerge instead of waiting 1 or 2 years for the field to agree that using a specific regimen is the correct thing to do.
Regular Exercise Could Help Prevent Liver Cancer
A team of researchers has found that regular exercise activates a gene that suppresses tumor growth of the most common type of liver cancer called Hepatocellular Carcinoma (HCC). The study was performed using mouse models. The team genetically modified the mice causing them to over-eat, become obese and develop type 2 diabetes. The mice were also previously injected with a cancer-causing agent. Half of the mice were allowed regular access to a running wheel, and ran up to 40 kms a day, while the other half were not and remained sedentary. Although the running mice slowed their weight gain, by six months into the experiment, even the running mice were obese. The team observed that at the 6-month mark most of the sedentary mice had liver cancer while none of the exercising mice had developed it.
Sequencing Targeted Therapies And Immunotherapies In Hepatocellular Carcinoma
The frontline treatment options for patients with Hepatocellular Carcinoma (HCC) include sorafenib (Nexavar) and lenvatinib (Lenvima). Regorafenib (Stivarga), cabozantinib (Cabometyx), and ramucirumab (Cyramza) are all FDA-approved as second-line, or future, treatments. Patients can also receive nivolumab (Opdivo) and pembrolizumab (Keytruda) as follow-up treatments. Doctors agree that the sequencing of treatments remains an important topic in the treatment landscape of HCC. According to Lipika Goyal, MD, “Immunotherapies are available as well and are useful in select patient populations, such as those who rapidly progressed on the tyrosine kinase inhibitors (TKIs) sorafenib or lenvatinib, had poor tolerability of the agents, or are unable to receive third-line therapy.” Goyal goes on further to explain that single-agent immunotherapy after someone has already received atezolizumab is unlikely to be effective and encourages these patients to consider enrolling in clinical trials.
Immunotherapy Combinations Emerge As Likely Standard For Future HCC Management
According to the phase III IMbrave150 study, the combination of PD-L1 and VEGF inhibition may be a treatment for Hepatocellular Carcinoma (HCC). The trial examined the combination of atezolizumab (Tecentriq) plus bevacizumab (Avastin) versus sorafenib (Nexavar). The study included 501 patients with unresectable HCC who were randomly assigned to 1200 mg of intravenous (IV) atezolizumab plus 15 mg/kg of IV bevacizumab every 3 weeks or 400 mg of sorafenib twice daily. The median progression-free survival (PFS) was 6.8 months in the atezolizumab/bevacizumab arm and 4.3 months in the sorafenib arm. The median overall survival (OS) was not reached in the atezolizumab/bevacizumab arm versus 13.2 months in the sorafenib arm.
Ghassan K. Abou-Alfa, MD, MBA discusses with several doctors the future of care for patients with Hepatocellular Carcinoma (HCC). He believes that understanding the etiologies, or the causes, is especially important as well. Ahmed Kaseb, MD explains that is it important for the care team to know how strong both the patient and the liver are before beginning a course of treatment. The next step is to personalize the treatment and choose a combination of therapy and create the appropriate sequencing. Anthony B. El-Khoueiry, MD believes that HCC is a broad disease where the use of biomarkers is key and the breakdown of the molecular subgroups.
Real-Life Analysis Of Nivolumab In Patients With HCC Align With Clinical Trial Data
Researchers emphasize the importance of early diagnosis and appropriate management of Hepatocellular Carcinoma (HCC), based on the data of a real-life cohort of patients receiving nivolumab (Opdivo). The study reviewed 118 patients from 10 institutions in Spain, with the most common adverse effects including hepatitis C (57.1%) and hepatitis B (11.9%). Corticosteroids were used for the management of most adverse effects. Nivolumab was used as frontline therapy in 7 patients, second-line in 20 patients, and third-line in 15 patients. At the last follow-up assessment, 25 patients remained alive, including 24 patients who continued to receive nivolumab, 17 patients had died, and 17 patients discontinued due to disease progression.
Shenogen and BioArdis have joined into a collaboration and licensing agreement for the development and commercialization of BioArdis' FGFR4 (fibroblast growth factor receptor 4) kinase inhibitor, BIO-1262/SNG-203, to be used as a monotherapy or combination therapy. BIO-1262 is being evaluated as a potential new treatment for Hepatocellular Carcinoma (HCC). Fibroblast growth factor receptors (FGFRs) play a key role in regulating cell survival and growth, and many recent studies suggest that they also play a role in cancer progression. Dr. Meng Kun, chairman of Beijing Shenogen Pharmaceutical Group, states, “Icaritin from Shenogen is currently in late-stage of phase III clinical trials for the treatment of advanced Hepatocellular Carcinoma (HCC) as a single agent and in combination therapies. The addition of clinical development of BIO-1262/SNG-203 will strategically solidify our company’s leading position in the field of Hepatocellular Carcinoma treatments.”
Yiviva, a clinical-stage biotechnology company developing multi-target botanical therapeutics using a systems biology approach, has dosed their first patient sin their Phase 2b study of YIV-906 in combination with sorafenib in the treatment of patients with hepatitis B-positive Hepatocellular Carcinoma (HCC). YIV-906 is a therapeutic candidate made up of a proprietary cGMP botanical extract of four herbs which are inspired by a traditional Chinese medicine formulation used for over a millennium. Yiviva shows that YIV-906 may have the ability to enhance the anti-tumor activity of sorafenib, protect cells of the gastrointestinal tract, and enhance natural and adaptive immune function. The clinical study is looking to enroll 125 patients within 20 sites in the U.S., mainland China, Hong Kong, and Taiwan.
MRI Identifies Biomarkers For Aggressive HCC Subtype
According to a recent study, a team of French researchers has discovered three important biomarkers to heighten the pre-operative detection of the macrotrabecular-massive subtype, an aggressive form of Hepatocellular Carcinoma (HCC). Led by Dr. Sébastien Mulé, Ph.D., from Henri Mondor University Hospital in Créteil, the team performed a retrospective study to analyze 152 patients who pre-operatively underwent a liver scan. All the patients had one HCC lesion, which was removed with surgical resection. Among them, the MRI identified 26 macrotrabecular-massive HCCs. The existence of substantial necrosis, high serum alpha-fetoprotein (AFP) levels, and a more advanced stage of liver cancer were independently associated with macrotrabecular-massive HCC.
FDA Approves Immunotherapy Combination For Liver Cancer
Based on results from the Phase I/II CheckMate 040 trial, the FDA approved the combination of checkpoint inhibitors Opdivo (nivolumab) and Yervoy (ipilimumab) for people with advanced Hepatocellular Carcinoma (HCC). The trials showed a response rate of 33% among HCC patients who had been previously treated with Nexavar (sorafenib), a tyrosine kinase inhibitor, which is typically a standard first-line treatment. Opdivo is a PD-1 checkpoint inhibitor that helps the immune system fight against cancer cells. Yervoy is a different type of checkpoint inhibitor that blocks CTLA-4, which turns off immune responses by suppressing T-cell replication.
New Drugs Approved For Liver Cancer Treatment
Bristol Myers Squibb has received approval from the FDA for its immunotherapy medications, Yervoy and Opdivo for the treatment of patients with Hepatocellular Carcinoma(HCC) who have been treated by sorafenib previously. Based on previous clinical trial results, 33% of participants had responded to the treatment. Nivolumab, another treatment approved for HCC may come with serious side effects, including colitis, renal dysfunction, and inflammation of the lungs. HCC is the most common type of liver cancer and has been on the rise in the US.
Dicerna Pharmaceuticals has been granted orphan drug designation by the FDA for DCR-A1AT for the treatment of alpha-1 antitrypsin (A1AT) deficiency. A1AT deficiency is a genetic disorder that can cause liver disease. Dicerna is a biopharmaceutical specializing in investigational ribonucleic acid interference (RNAi) therapeutics. A1AT is a protein produced in and released from the liver. “RNAi technology has shown significant potential in the treatment of liver-related diseases, and we look forward to continuing to investigate DCR-A1AT’s potential to make a meaningful difference for this underserved patient population,” said Ralf Rosskamp, M.D., chief medical officer of Dicerna. Dicerna has submitted a clinical trial application to the Swedish Medical Products Agency for DCR-A1AT for the treatment of patients with A1AT deficiency-associated liver disease and began has already begun enrolling healthy volunteers in the Phase 1/2 trial of DCR-A1AT.
Liver Cancer Symptoms: An Uncomfortable Sign On The Skin Could Signal The Disease
Liver cancer develops when abnormal cells start to divide and grow in an uncontrolled way in the liver, and the earlier it is detected, the better the chance of survival is. Unfortunately, cancer is often detected in advanced states. Cancer has several external symptoms. Some warning signs are frequent hiccups, itchy skin, and jaundice. Other serious indications may be loss of appetite, feeling very full after eating any size meal, and pain or swelling in the abdomen. A color change in stool may also indicate something is wrong.
Can-Fite Biopharma Ltd has already enrolled 7 patients for the compassionate use program for Namodenoson in the treatment of hepatocellular cancer (HCC) led by Dr. Salomon Stemmer, Professor at the Institute of Oncology, Rabin Medical Center, Israel. Namodenoson is a small oral drug that binds with high affinity and selectivity to the A3 adenosine receptor (A3AR). Can-Fite has also submitted a Phase III protocol and Registration Plan to the European Medicines Agency (EMA) for Namodenoson. The completed Phase II trial as a second-line treatment found Namodenoson to have a good safety profile and was well tolerated.
HCC Treatment Continues To Improve, But Biomarkers Are Still Needed
The past few years have seen a large increase in targeted therapies and immunotherapy options to treat Hepatocellular Carcinoma (HCC). Doctors now will need to focus on the proper sequencing of these treatments which will be most effective for their patients. Earlier this year a supplemental biologics license application (sBLA) was submitted to the FDA for the combination of atezolizumab (Tecentriq) and bevacizumab (Avastin) as a treatment, based on the results of the phase III IMbrave150 trial in which the median overall survival (OS) was not reached with the combination as compared with 13.2 months with sorafenib. In 2019 regorafenib and cabozantinib (Cabometyx) were approved for treatment as well.
FDA Approves Nivolumab Plus Ipilimumab In Advanced Hepatocellular Carcinoma
Recently the FDA granted accelerated approval to the combination of nivolumab (Opdivo) and ipilimumab (Yervoy) for the treatment of patients with Hepatocellular Carcinoma (HCC) who were previously treated with sorafenib (Nexavar). The overall survival (OS) of patients using nivolumab and ipilimumab as a second-line treatment of HCC showed promising results based on the CheckMate-040 clinical trial which included a total of 148 patients. Results from that trial showed that of the 33% of patients who responded to treatment with the combination, 8% had a complete response and 24% had a partial response, at the 28 months. Additionally, patients who received 6 months of sorafenib or more experienced an overall response rate of 36.4%.
According to the results of a retrospective study, low-dose aspirin use was associated with significantly lower risk for Hepatocellular Carcinoma (HCC) among patients with chronic viral hepatitis. Experimental and clinical data show that aspirin may prevent liver disease progression and hepatocarcinogenesis, the production of cancer in the liver. It works by preventing platelet break-down, modulating bioactive lipids and inhibiting inflammation. The retrospective study analyzed over 14.000 Swedish patients diagnosed with Hepatitis B or C and no history of aspirin use. Results showed an estimated 10-year cumulative incidence of HCC of 4% among aspirin users and 8.3% among nonusers. Further analysis showed aspirin users had a 31% lower risk for HCC than nonusers.
Optimizing Treatment Approaches For Hepatocellular Carcinoma
“Patients with HCC often shift from locoregional or radical care to palliative care, which makes it crucial that physicians have an ongoing multidisciplinary effort when managing these patients,” says David J. Pinato, MD, PhD of the Department of Surgery and Cancer, Imperial College London. According to Pinato, it is important for doctors to use a multidisciplinary approach when treating patients with HCC. AS more treatments are approved, researchers will look for a link between good management of underlying liver function with good oncologic management.
Chinese Biotech Startup Genfleet Closes $58m In Series B Round
GenFleet Therapeutics, a Shanghai-based pharmaceutical company, is currently developing GFH018, a small molecule inhibitor for the treatment of Hepatocellular Carcinoma (HCC). The Phase 1 trial has already begun in Shanghai. The clinical trial application of GFH018 has been approved by China’s Center for Drug Evaluation (CDE), said Lu Qiang, chairman and founder of GenFleet. GenFleet was able to raise $17 million in a Series A round led by Ally Bridge Group, a healthcare-focused investment company founded by former Goldman Sachs executive Frank Yu. Proceeds of the Series B round will be used to finance overseas registration and clinical trials.
Liquid Biopsy May Play A Role In Identifying Markers Of Response In HCC
According to Augusto Villanueva, MD, assistant professor of the Division of Liver Diseases at the Tisch Cancer Institute of Icahn School of Medicine at Mount Sinai Hospital, Hepatocellular Carcinoma (HCC) lacks in identifying markers of response and genetic drivers. Liquid biopsies can help in finding biomarkers. Also, analyzing plasma can help physicians detect driver genes more effectively and efficiently. Researchers use the circulating tumor cells to help provide more information on potential biomarkers. Villanueva states, “In the last 10 years, we have gained a significant understanding of the driver mutations in HCC. The most prevalent mutations are TERT promoter, TP53, β-catenin.”
Roche Gets U.S. Breakthrough Tag For Liver Cancer Diagnosis Approach
Roche Diagnostics has developed the Elecsys GALAD score, which combines factors including age, gender and biomarker results to more quickly and accurately diagnose early-stage Hepatocellular Carcinoma (HCC. This diagnostic approach has been given Breakthrough Device Designation by the FDA. Roche is also working on a combination treatment using Tecentriq and Avastin, which has been submitted for FDA approval. "The combination of blood-based biomarkers with clinical algorithms has the potential to significantly reduce mortality of HCC patients as they can receive a timelier diagnosis and treatment," said Roche Diagnostics head Thomas Schinecker.
Doctors Testing New Liver Transplant Transport System
Intermountain Healthcare officials are currently testing a new liver transport system called the hypothermic machine perfusion pump, which could save patients on the transplant list by better preserving the organs in transit. The standard way of transporting a liver involves placing the liver in a bag of special fluid and packing it in ice in a cooler. The new pump is considered an “active” transportation, as the case that the liver is in has what a liver needs to keep working. The pump circulated perfusion solution through the liver to eliminate stagnant blood. Jake Krong is the research manager at Intermountain Transplant Services. Intermountain Healthcare is participating in clinical trials with five other transplant centers.
Biomarkers, Patient Factors Inform HCC Treatment Decisions Beyond Frontline Setting
Lipika Goyal, MD, an instructor at Harvard University Medical School, stated, “There are clear biomarkers available to guide treatment decisions in the second-line setting for patients with advanced Hepatocellular Carcinoma (HCC). Goyal refers to the phase III IMbrave150 trial including atezolizumab (Tecentriq) and bevacizumab (Avastin) the "-1 line of therapy" because the combination has not been FDA approved. She also believes that for patients who have already received the combination of atezolizumab/bevacizumab, Yttrium-90 (Y-90) embolization may be a viable option, before proceeding to sorafenib (Nexavar) or lenvatinib (Lenvima). Based on the data from the phase III RESORCE trial, it was the first to demonstrate a survival benefit for a systemic therapy in the second-line setting for patients with advanced HCC who progressed on sorafenib.
El-Khoueiry Forecasts Future Of HCC Treatment Paradigm
Anthony El-Khoueiry, MD, assistant professor of clinical medicine at the Keck School of Medicine at the University of Southern California, believes that by 2025 there will be many more approved drugs and drug combinations for the treatment of advanced Hepatocellular Carcinoma (HCC). Currently, there are only 2 first-line treatments, which are used, sorafenib (Nexavar) and lenvatinib (Lenvima). A front-line combination therapy is atezolizumab (Tecentriq) plus bevacizumab (Avastin). Second-line therapies include regorafenib (Stivarga), nivolumab (Opdivo), and pembrolizumab (Keytruda). El-Khoueiry stresses that the drug development companies should address molecular heterogeneity more closely.
Recent Approvals, Collaborative Care Model Spark Change In HCC Treatment
Michael R. Charlton, MD believed that the study of Hepatocellular Carcinoma (HCC) is moving toward a more comprehensive, personalized, and optimistic approach in treatment due to the new therapies and potential biomarker discoveries. In addition, the care team of the patient now includes an oncologist, a radiologist, and a surgeon so that their collaboration can offer the best treatment options. Charlton hopes to see more patients screened early, in the future, so that if they are diagnosed, they may be treated with resection or locoregional therapy.
Medivir AB recently conducted a phase IA study with MIV-818 , an orally administered drug, to evaluate safety and tolerability in liver cancer patients. Two of the nine patients involved in the study had Hepatocellular Carcinoma (HCC). Biomarker analysis of liver biopsies showed a selective liver cancer effect of MIV-818, where the tumor tissue had clear DNA damage while healthy liver tissue showed only minimal or no DNA damage. The analysis of data from the nine patients confirms the researchers' conclusion that the continued development of MIV-818 as a new and effective treatment for liver cancer would be beneficial.
Immunotherapy Combinations Show Promise in Advanced HCC
El-Khoueiry, associate professor of medicine at USC Norris Comprehensive Cancer Center, explains that there are several reasons why monotherapy trials have failed, including the idea that a single agent therapy might not be enough to treat Hepatocellular Carcinoma (HCC). El-Khoueiry expresses the importance for anti-VEGF agents and tyrosine kinase inhibitors (TKIs) to work together, based on previous research which shows that targeting the VEGF axis leads to decreases in the activity of inhibitory cells, increased PD-L1 expression, and enhanced T cell tumor infiltration and activation. The combination of atezolizumab (Tecentriq) and bevacizumab (Avastin) demonstrated strong efficacy as first-line therapy in patients with unresectable HCC.
Evidence Illustrates Multidisciplinary Care Is Standard In HCC
Amit G. Singal, MD, medical director of the Liver Tumor Program at The University of Texas Southwestern (UTSW) Medical Center, encourages treatment for patients with Hepatocellular Carcinoma (HCC) which incorporates multiple providers from a variety disciplines as it may lead to better results. Based on previous research, underuse or the delays of optimal HCC treatment are associated with worse survival outcomes. A retrospective cohort study including 267 treatment-eligible patients showed a median time to treatment as 1.7 months. Singal stressed that optimal timing of appropriate therapy is key in HCC management.
Biomarker Hunt Gains Traction Among Therapeutic Advances In HCC
David J. Pinato, MD, Ph.D., states "This is a moment of dramatic change in HCC care. [The lack of biomarkers] was [a result of] a vicious circle. Patients were not routinely biopsied because there were no alternative therapies to offer them. That led to a lack of updated knowledge of the molecular pathophysiology of liver cancer. Then, that led to a lack of biomarkers for these patients." the team of researchers continue to search for the optimal markers that could predict response to the growing number of therapies. PD-L1 expression for immunotherapy and FGF19 expression another potential target being explored is are currently being explored.
Dr. Parikh On The Importance Of Multidisciplinary Care In HCC
According to Neehar Parikh, MD, medical director and assistant professor at the University of Michigan, patients with Hepatocellular Carcinoma (HCC) are commonly treated by a multidisciplinary team in the university setting, including hepatologists, interventional radiologists, oncologists, diagnostic radiologists, and palliative care specialists. The care team works as a single unit to optimize treatment for patients and address any complications that may develop. Studies show that there is a survival advantage when patients who receive curative intent therapy are treated by a multidisciplinary team compared with those treated by a single physician.
Abou-Alfa Hails "Positive And Disruptive" Impact Of Novel Combinations In HCC
Results of the phase III IMbrave 150 trial showed that the combination of atezolizumab (Tecentriq) plus bevacizumab (Avastin) improved overall survival (OS) versus sorafenib (Nexavar) in patients with Hepatocellular Carcinoma (HCC). At the 8.6-month follow-up, researchers saw a 42% decrease in the risk of death and a 41% decrease in the risk of disease progression or death in the atezolizumab/bevacizumab arm versus sorafenib. The median progression-free survival (PFS) was 6.8 months with combination therapy and 4.3 months with sorafenib alone. Ghassan K. Abou-Alfa, MD., a medical oncologist at Memorial Sloan Kettering Cancer Center, said the combination will overtake sorafenib as the standard of care in the first-line setting at some point.
Can-Fite BioPharma Ltd. in collaboration with Univo Pharmaceuticals, has published pre-clinical findings showing the inhibiting characteristics which CBD has against liver cancer. The results are based on studies utilizing human liver cancer cells. UNIVO produces its own cannabis through a partnership with Amit Farms, located in Israel. The agreement with Univo Pharmaceuticals includes testing of minute CBD dosages in combination with Namodenoson on liver cancer.
Prevention Signal For Statins In Liver Cancer Supports Prophylaxis
According to the investigator, statins have shown to provide significant protection against liver cancer and should be considered in patients at high risk. Muhammad T. Sarmini, MD, a gastroenterologist affiliated with the Cleveland Clinic in Cleveland, stated that the analysis of 20 studies with approximately 2.6 million patients worldwide, showed that the use of the cholesterol agents was associated with a 43% reduction in the risk for Hepatocellular Carcinoma (HCC). Upon categorizing the studies, the team found that the risk reduction for statins was 47% for case-control studies and 37% for cohort studies.
Abivax SA is currently conducting a Phase 1/2 clinical trial of ABX196 to treat patients with Hepatocellular Carcinoma (HCC). The study will gather data to determine the safety, efficacy and tolerability of the treatment on its own and in combination. The teams of researchers at two MD Anderson Cancer Centers have shown that ABX196 and the combination of ABX196 and a checkpoint inhibitor, showed a statistically highly significant therapeutic effect in reducing tumor growth as measured by MRI and increasing survival in mice models. ABX196 is intended to enhance the efficacy of checkpoint inhibitors by activating iNKT cells to kill tumor cells.
ARID2 Suppresses Hepatocellular Carcinoma Metastasis Via DNMT1-Snail Axis
Dr. XIE Dong of the Shanghai Institute of Nutrition and Health of the Chinese Academy of Sciences recently published the results of his study on the role and mechanism of AT-rich interactive domain 2 (ARID2) in liver cancer metastasis, providing therapeutic targets for the treatment of Hepatocellular Carcinoma (HCC). The team found that ARID2 expression was significantly decreased in metastatic HCC tissues, and showed a negative correlation with organ metastasis and positive association with survival of HCC patients. Based on HCC mouse models, ARID2 knockout promoted pulmonary metastasis, secondary malignant tumors.
Tetra In Manufacturing Deal For Printed CBD Treatment
Tetra Bio-Pharma has signed an agreement with Vitiprints for the commercial manufacture of two CBD-based drug candidates, Caumz (synthetic tetrahydrocannabinol (THC) and cannabidiol (CBD)) and HCC011 (inhaled delta-9-THC). Caumz is currently at Phase II and HCC011 is being investigated at the same stage for Hepatocellular Carcinoma (HCC). This collaboration will increase production from 2,500 dosing capsules in a three-day period to 100,000 dosage units in a single eight-hour period. Vitiprints specializes in 2D printing technology and will provide Tetra Bio-Pharma with an exclusive license for the commercial production of its two drug candidates, for use within a vaporizing system, Caumz-kit.
Hepatocellular Carcinoma: 5 Things To Know
Patients who are at risk or have been diagnosed with Hepatocellular Carcinoma (HCC) have any things to consider. It is important to keep in mind that cirrhosis is the biggest risk factor for HCC. One third of all patients with cirrhosis will develop HCC. Check-ups are recommended every six months. Fatty liver is another major factor contributing to the rise in HCC incidence. Patients also need to be aware that treating chronic hepatitis infection reduces the risk for HCC but does not eliminate it. Curing chronic hepatitis C infection is associated with a 71% risk reduction of HCC.
Can-Fite Submits Liver Cancer Phase III Protocol and Registration Plan to EMA for Namodenoson
Can-Fite BioPharma Ltd. has begun a Phase III trial to evaluate the efficacy of Namodenoson in patients with advanced Hepatocellular Carcinoma (HCC). The FDA approved Can-Fite’s proposed Phase III trial design to support a New Drug Application (NDA) submission and approval of Namodenoson for the treatment of HCC. Namodenoson is a small oral treatment that binds with high affinity and selectivity to the A3 adenosine receptor (A3AR). Can-Fite is biotechnology company that develops small molecule drugs for the treatment of cancer and liver disease.
Recently many new combination therapies have come to light for the treatment of patients with advanced Hepatocellular Carcinoma (HCC). Combination treatment of atezolizumab (Tecentriq) plus bevacizumab (Avastin) showed better patient-reported outcomes than treatment with sorafenib (Nexavar) in patients with HCC. The triple combination therapy using nivolumab (Opdivo), ipilimumab (Yervoy), and cabozantinib (Cabometyx) provided clinically meaningful responses in patients with advanced HCC who were treatment-naïve or intolerant of sorafenib. Therapy combination nivolumab plus cabozantinib reported a median progression-free survival (PFS) of 5.4 months and median overall survival (OS) of 21.5 months.
AVEO Oncology is developing a new treatment called FOTIVDA (tivozanib), for the treatment of patients with advanced, inoperable Hepatocellular Carcinoma (HCC). A total of 27 patients are enrolled in the Phase 1b/2 trial. Median progression-free survival (PFS) was 24 weeks and overall survival (OS) was 9 months, for patients treated at the recommended Phase 2 dose (RP2D) of 1.0 mg once daily for 21 days. Tivozanib has been shown to reduce regulatory T-cell production in preclinical models. Enrollment has begun in a Phase 1b/2 DEDUCTIVE study of tivozanib in combination with AstraZeneca’s IMFINZI® (durvalumab). Tivozanib is a vascular endothelial growth factor receptor (VEGFR) tyrosine kinase inhibitor (TKI).
STIVARGA (Regorafenib) For Patients With Unresectable Hepatocellular Carcinoma
Regorafenib is approved for the treatment of patients with Hepatocellular Carcinoma (HCC) who have previously been treated with sorafenib. Based on results from the Phase 3 RESORCE trial, regorafenib was shown to increase overall survival. Regorafenib is a multi-kinase inhibitor that blocks multiple protein kinases involved in tumor angiogenesis, the development of new blood vessels, and oncogenesis, the growth of new tumors. The treatment is taken orally. There are currently further ongoing trials for HCC patients with unresectable tumors.
Dr. Abou-Alfa On Progress Made In Hepatocellular Carcinoma
Ghassan K. Abou-Alfa, MD, medical oncologist at Memorial Sloan Kettering Cancer Center, believes that there has been very much progress made in the treatment of patients with Hepatocellular Carcinoma (HCC). Sorafenib (Nexavar) is 1 of 7 treatments to receive regulatory approval in HCC, says Abou-Alfa. Sorafenib and lenvatinib (Lenvima) are first-line options. “In the second-line setting, regorafenib (Stivarga), which is conditional on prior sorafenib exposure, cabozantinib (Cabometyx), and ramucirumab (Cyramza), which requires high alpha-fetoprotein are also approved for use. In addition, nivolumab (Opdivo) and pembrolizumab (Keytruda) are approved for use as monotherapy following prior exposure to sorafenib,” Abou-Alfa explains.
Real-World Study Shows Snapshot Of A Survival Gap With Existing Therapies For Patients With HCC
According to a recent study, patients with Hepatocellular Carcinoma (HCC) who receive systemic therapy have a poor prognosis in the community practice setting. The team looked at over 2000 patients treated with treatments including transplant, stereotactic body radiation therapy (SBRT), radiofrequency ablation (RFS), transarterial chemoembolization (TACE), and a tyrosine kinase inhibitor (TKI) with median overall survival (OS) of 16.6 months. Treatment with a TKI had the lowest OS benefit at 5.0 months, and transplantation had the highest benefit at 71.5 months. Michael A. Morse, MD, heading the study explained that it may not be practical for community oncologists to follow the treatment standards born from clinical trials because average patients with HCC do not have the same outcomes as patients who undergo treatment in the clinical trial setting.
MRI Contrast Agent Detects Early Stage Liver Cancer
A team of researchers led by Jenny Yang, a professor at Georgia State University and associate director of the Center for Diagnostics and Therapeutics, has identified a new biomarker for detection of liver metastases. They have developed an agent that can target chemokine receptor 4 (CXCR4) which becomes over-expressed in the liver for people with cancer. Researchers expect the CXCR4 targeted protein-based MRI contrast agent will be able to detect even tiny instances of cancer cells on multi-color scans called precision MRI (pMRI) imaging. The team used gadolinium in the MRI and found that protein design is much more effective in targeting the signs of disease.
Cerium Oxide Nanoparticles May Improve Hepatocellular Carcinoma Prognosis
A team of researchers from the Institut d'Investigacions Biomèdiques August Pi Sunyer (IDIBAPS) and from the Catalan Institute of Nanoscience and Nanotechnology (ICN2) have been working together to create an effective treatment for Hepatocellular Carcinoma (HCC) using cerium oxide nanoparticles. Cerium oxide nanoparticles have antioxidant and anti-inflammatory properties have shown to partially reverse the cellular mechanisms involved in tumor progression and have significantly increased survival in a rat animal model. The animal models showed that rats treated with the nanoparticles had fewer cancer nodules in the liver, had reduced levels of the cancer biomarker alpha-fetoprotein, showed less proliferation of the cancer cells and more apoptosis cell death. The study also showed that treated rats have double the survival time of the untreated rats.
The FDA has granted orphan drug designation to STP705 (Cotsiranib) for the treatment of Hepatocellular Carcinoma (HCC). STP705, created by Sirnaomics, Inc., is a siRNA (small interfering RNA) therapeutic that targets the polypeptide nanoparticle (PNP) to enhanced delivery and destroy the TGF-β1 and COX-2 gene expression. In preclinical animal trials, STP705 has shown a considerable improvement in T-cell penetration into tumors in the liver, and improvement in the efficacy of an anti-PD-L1 antibody checkpoint inhibitor in an HCC model. "This orphan drug designation aligns with our mission to alleviate human suffering and target diseases with high unmet clinical need and we anticipate the start of our clinical study for HCC in the second half of 2020," said Dr. Michael Molyneaux, MD, MBA, Chief Medical Officer.
Geneos To Test GNOS-PV02 Cancer Vaccine In Triple Combo Trial For Advanced Liver Cancer
GT-30 trial (NCT04251117), a Phase 1/2 trial of a triple immunotherapy combination for the treatment of patients with advanced Hepatocellular Carcinoma (HCC) is being initiated by Geneos Therapeutics. The trial involves their patient-specific cancer vaccine GNOS-PV02. The trial will include 12 HCC patients to test the combination of GNOS-PV02, the immune system modulator INO-9012, and the immune checkpoint inhibitor Keytruda (pembrolizumab). GNOS-PV02 is a personalized cancer vaccine that elicits strong immune responses. INO-9012 is designed to reinforce the activation and expansion of immune T-cells. Keytruda, which is developed by Merck, is an immune checkpoint inhibitor that prevents cancer cells from evading the immune system.
Cancer Breakthrough Raises Hopes Of Early Diagnosis For Liver Cancer
A team of researchers including Professor Jenny Yang, of Georgia State University and Dr. Alexis Webb, of Cancer Research UK, have proven through experiments with mouse models, that liver cancer can be detected at stage two rather than stage four. Stage two liver cancer is defined as a tumor that is more than 2cm in size and has grown into the blood vessels of the liver. Current testing with biopsy is often done too late, and the cancer is too far along for curative treatment. The team's new method involves injecting a chemical that targets cancer cells and uses a metal element within it. The targeted cancer cells can then which can be seen on an MRI scan. The FDA is currently fast-tracking this new method for clinical trials in humans.
Hi-Precision Diagnostics Launches New Test Panel For Better Liver Cancer Detection
Hepatitis B affects an estimated 10 percent of Filipinos and is the most common cause of Hepatocellular Carcinoma (HCC) or primary cancer of the liver in the Philippines. HCC is the second most common cause of cancer death in the Philippines as most patients are diagnosed too late for curative treatment. Hi-Precision Diagnostics, a medical laboratory, launched the HCC Risk Panel at the 2020 Philippine Liver Meeting, specifically directed to the delegates of the Hepatology Society of the Philippines as a new tool for early liver cancer detection. The panel is performed by testing blood samples to measure all three markers with the µTASWako i30 platform. Dr. Hiroyuki Yamada, Ph.D., Fujifilm Wako Pure Chemicals representative, discussed how more comprehensive tumor marker screening including AFP, AFP L3, and DCP has improved liver cancer detection and survival in Japan.
Combination Atezolizumab Plus Bevacizumab Improved Quality Of Life In HCC
The phase III IMbrave 150 clinical trial evaluated the combination of atezolizumab (Tecentriq) plus bevacizumab (Avastin) versus the standard of care, sorafenib (Nexavar), as the frontline treatment Hepatocellular Carcinoma (HCC). Peter R. Galle, MD, the director of the Medical Department at the University Medical Center Mainz explains, “These findings showed that a lower proportion of patients with unresectable HCC had deterioration of quality of life (QoL) with the combination atezolizumab plus bevacizumab compared with sorafenib.” The combination showed time to deterioration of QoL was 11.2 months in the combination arm versus 3.6 with sorafenib, and an extended median time to several symptoms.
Immunitor Publishes Interim Results From Phase III Trial Of Oral Immunotherapy For Liver Cancer
Mongolia has the highest incidence of Hepatocellular Carcinoma (HCC). As HCC is on the rise the FDA has recently approved three antibody-based drugs for HCC indication: nivolumab, pembrolizumab, and ramucirumab. Previous experiments show that none of the currently approved or experimental HCC drugs are free from adverse side effects, and unfortunately have limited effect in shrinking tumors. Developed by Vancouver-based Immunitor Inc in collaboration with the medical team at the National Cancer Center in Mongolia and investigators in the USA, China and Thailand the therapeutic vaccine called hepcortespenlisimut-L (V5 or Hepko-V5) was successful in a 75-patient Phase II trial in 2017. The anti-HCC property of V5 was discovered accidentally ten years and has been used by over 30,000 individuals since 2002 and has never been reported of causing any serious adverse reactions.
The Role Of The Innate Immune System In The Development And Treatment Of Hepatocellular Carcinoma
Scientists are currently studying the role of the innate immune system in the development and treatment of Hepatocellular Carcinoma (HCC). The innate immune system is responsible for immune cells infiltrating solid tumors or the tumor microenvironment. The functionality of innate cells is regulated by several factors, including pro- and anti-inflammatory cytokines as well as fibroblasts. Patients with advanced cancer stages who are not eligible for surgical treatment are recommended palliative drug therapies including tyrosin kinase inhibitors (TKI) such as sorafenib, lenvatinib, regorafenib or cabozantinib. Unfortunately, these treatments only offer minimal survival benefits and are regarded as not cost-effective strategies for HCC treatment.
The Impact Of Liver Pathobiology On HCC Treatment Approach
Ghassan K. Abou-Alfa, MD explains the importance of recognizing that there are specific targets that should be attacked regarding liver cancer. Most of those usually are taken care of by tyrosine kinase inhibition. The role of immunotherapy or checkpoint inhibitors in liver cancer is also very important. A checkpoint inhibitor like an anti–PD-1 [anti–programmed cell death protein 1], like nivolumab or pembrolizumab, has not yet been proven to be more beneficial than a tyrosine kinase inhibitor for patients with liver cancer. The combination of checkpoint inhibitors plus a tyrosine kinase inhibitor is another category of treatment options.
Lenvatinib Appears Effective In Real-Life Retrospective Analysis Of Advanced HCC
In a retrospective multicenter observational analysis in Korea, the tyrosine kinase inhibitor lenvatinib (Lenvima) demonstrated promising activity and safety in patients with advanced Hepatocellular Carcinoma (HCC). The overall response rate (ORR) was 10.7%. for a total of 75 patients according to RECIST. At a median follow-up of 4.7 months, the median overall survival (OS) was 6.7 months. Stable disease (SD) was observed in 50 patients overall. A complete response (CR) was not observed in any patients, but 8 patients in the overall population had a partial response (PR).
Dr. Villanueva On Eliminating Tumor Heterogeneity In Patients With HCC
Augusto Villanueva, MD, an assistant professor of the Division of Liver Diseases at the Tisch Cancer Institute of Icahn School of Medicine at Mount Sinai Hospital presented mutations and gene signatures for patients with Hepatocellular Carcinoma (HCC) at the 2020 Gastrointestinal Cancers Symposium. Villanueva's showed a significant connection to the composition of the tumor microenvironment and the heterogeneity at the level of gene expression. He hopes that liquid biopsies may play a role in obtaining new biomarkers for HCC. Previous research shows that analyzing plasma can make it easier to detect driver genes in patients with HCC. DNA, RNA, and microRNA can be analyzed to provide biomarkers for HCC.
Roche Files Tecentriq/Avastin Combo In Liver Cancer
Based on the results from the IMbrave150 study for Hepatocellular Carcinoma (HCC) Roche has filed Tecentriq (atezolizumab) in combination with Avastin (bevacizumab) as a first-line treatment. The IMbrave150 study involved patients who could not be treated with surgery and who had not been treated with any other systemic therapy. Patients received PD-L1 inhibitor Tecentriq plus anti-VEGF antibody Avastin or Bayer’s Nexavar (sorafenib) – a standard first-line therapy. According to Roche’s chief medical officer Levi Garraway, if Roche wins approval, the Tecentriq/Avastin regimen would be the first therapy to extend survival in first-line HCC treatment for more than a decade.
Exelixis, Inc. has been conducting CheckMate 040, a phase ½ clinical trial testing the combination of cabozantinib (CABOMETYX®) and nivolumab (Opdivo®) with or without ipilimumab (Yervoy®) in advanced Hepatocellular Carcinoma (HCC). For the 36 patients treated with the combination of cabozantinib and nivolumab showed a 75% disease control rate (DCR), median progression-free survival (PFS) of 5.4 months, and median overall survival (OS) of 21.5 months. For the 35 patients treated with the combination of cabozantinib, nivolumab and ipilimumab DCR was 83%, the median PFS was 6.8 months, and median overall survival has not yet been reached. Adverse side effects were observed in 47% of the cabozantinib and nivolumab group, and 71% of the cabozantinib, nivolumab and ipilimumab group. These side effects included diarrhea, hypertension, and lipase increase.
Patients With HCC Experience Better OS With Anticancer Procedure After Lenvatinib
Based on the results of the REFLECT trial, patients with unresectable Hepatocellular Carcinoma (HCC) experienced prolonged overall survival (OS) with lenvatinib (Lenvima) followed by an anticancer procedure, as opposed to sorafenib (Nexavar). Patients treated with lenvatinib demonstrated a median OS of 23.0 months compared with 9.6 months with sorafenib. Those who received subsequent anticancer procedures and/or medications had longer OS compared with those who did not. In the lenvatinib group, median OS was 19.5 months in those who received subsequent anticancer procedures and/or medications compared with 17.0 months in the sorafenib-treated patients who received subsequent anticancer therapy.
Lenvatinib Yields Promising Results In Unresectable HCC
Based on a retrospective analysis of a phase III clinical trial and the tyrosine kinase inhibitor (TKI) lenvatinib (Lenvima), both showed similar efficacy in patients with Hepatocellular Carcinoma (HCC). The study included 116 patients. 28 patients received lenvatinib as a second-line treatment, and 17 patients received the drug in the third line after second-line regorafenib. 49 patients were evaluated at weeks 4 to 8and found that 3 patients experienced a complete response, 14 patients had a partial response, 23 patients had stable disease, and 6 patients had progressive disease.
Atezolizumab In Combination With Bevacizumab May Be Effective For Patients With HCC
Results from the IMbrave 150 clinical trial testing the safety and efficacy of atezolizumab (Tecentriq) plus bevacizumab (Avastin) reported high-quality patient outcomes for patients with unresectable Hepatocellular Carcinoma (HCC). The lead author is Peter R. Galle, MD, PhD, from the University Medical Center in Mainz, Germany. The primary endpoint for the study was overall survival, in which patients were randomized 2:1 to receive either atezolizumab plus bevacizumab or sorafenib (Nexavar) alone as a first-line treatment. The median overall survival had not been reached for atezolizumab plus bevacizumab compared with the overall survival of 13.2 months in patients receiving sorafenib alone. The overall response rate was 27% with atezolizumab plus bevacizumab and 12% for the patients receiving sorafenib.
AstraZeneca’s Combination Treatment For HCC Snags Orphan Drug Designation
The U.S. Food and Drug Administration has granted Orphan Drug designation to AstraZeneca’s Imfinzi (durvalumab) and tremelimumab, an anti-CTLA4 antibody and potential new medicine, for the treatment of Hepatocellular Carcinoma (HCC). The combination of Imfinzi and tremelimumab is being studied as a treatment for HCC in the Phase III HIMALAYA trial. The trial is also assessing Imfinzi as a stand-alone treatment for HCC with results of each being compared to previous treatment results of Nexavar (sorafenib). Imfinzi is a human monoclonal antibody that binds to PD-L1 and blocks the interaction of PD-L1 with PD-1 and CD80. Tremelimumab blocks the activity of CTLA-4, contributing to T cell activation and boosting the immune response to cancer.
Minimally Invasive Liver Cancer Treatment Improving Quality Of Life For Patients
Y90 is a minimally invasive procedure used for the treatment for liver cancer with promising results. Interventional radiologist Dr. Dan Bozarth explained, “Not all tumors respond to chemotherapy, so not using chemotherapy but instead using radiation…. it’s way better tolerated than some of the other therapies.” Using x-rays for guidance, the procedure involves inserting a catheter filled with beads of radiation into a blood vessel in the leg which feeds into a cancerous tumor. The beads contain the radioactive Isotope Yttrium 90, which is sent directly to the tumor through that blood vessel. This treatment has been recommended for patients who do not respond to chemotherapy.
Combination Therapy Trial For Locally Advanced, Metastatic HCC Underway
CStone Pharmaceuticals and Blueprint Medicines Corporation are conducting a phase 1b/2 trial of fisogatinib in combination with CS1001 for the treatment of locally advanced or metastatic Hepatocellular Carcinoma (HCC). Fisogatinib is a potent and highly selective inhibitor of fibroblast growth factor receptor 4 which was discovered by Blueprint Medicines. Results from an ongoing phase 1 trial show that fisogatinib monotherapy was clinically active and well-tolerated in patients with heavily pretreated advanced HCC. CS1001 is an investigational anti-PD-L1 monoclonal antibody under development by CStone for multiple types of cancer.
Heterogeneity Of Liver Cancer Cells Helps Explain Tumor Progression In Patients
Based on a report from a team of researchers at Mount Sinai, liver cancer tumors contain a diverse set of cells, known as intra-tumor heterogeneity, which can significantly affect the rate at which the cancer grows. They reported that this heterogeneity, either within the same tumor or between different tumor regions in the same tumor nodule, appears in about 30% of patients with Hepatocellular cancer (HCC). So far two phase II clinical trials using PD-1 immune checkpoint inhibitors, which help the body's immune system recognize and attack cancerous cells, have achieved positive results in humans. Another phase III clinical trial, which combined a PD-1 immune checkpoint inhibitor with an antiangiogenic, showed to improve survival when compared to sorafenib.
Two Cancer-Causing Genes Work Together To Promote Metastasis
Two genes, MYC and TWIST1, have been previously identified to promote the growth and spread of cancer. Renumathy Dhanasekaran, a PhD student in the Division of Gastroenterology and Hepatology at Stanford University, states, "The main goal of our research is to understand how cancer-causing genes enable metastasis and use that information to identify targeted therapies that may prevent it." Dhanasekaran and team genetically engineered mice to express MYC and TWIST1 and found that these two genes led to metastases. They also observed that the cancer cells produced inflammation-promoting molecules Ccl2 and Il13, which attract immune cells called macrophages and make them more tumor-cell friendly, making it easier for the cancer cells to migrate to new areas of the body. The team then monitored Ccl2 and Il13 levels in 25 patients with liver cancer and 10 control patients with cirrhosis. They found that only the patients with liver cancer had elevated levels of the two molecules and those with higher levels of Il13 were more likely to have aggressive tumors.
Currently, the recommended treatment for patients with intermediate-stage Hepatocellular Carcinoma (HCC) is transarterial chemoembolization (TACE). Unfortunately, TACE is not suitable for patients with high-tumor-burden HCC. Past research shows that lenvatinib has demonstrated significantly and clinically meaningful anticancer efficacy by reducing tumor size. In a recent trail, 30 patients previously treated with lenvatinib or TACE were observed. The median progression-free survival (PFS) was 16 months in the lenvatinib arm and 3 months in the TACE arm. The median overall survival (OS) was 37.9 months in the lenvatinib arm and 21.3 months in the TACE arm.
TriNav™ Infusion System is the newest therapy enhancer designed by TriSalusTM Life Sciences, powered by its Pressure-Enabled Drug DeliveryTM (PEDD™) approach with SmartValveTM technology. TriNav is designed to help overcome the infusion barriers that limit therapeutic uptake in solid tumors in Hepatocellular Carcinoma (HCC). The tumor microenvironment creates pressure barriers that limit flow into solid tumors, but SmartValve creates a high-pressure gradient that improves delivery and penetration of therapy into tumors. The porous SmartValve is designed to use blood flow to carry the dose deep into a solid tumor. In a study, PEDD with SmartValve demonstrated the ability to overcome tumor infusion barriers and significantly improve response rates in HCC.
Machine Keeps Human Livers Alive For One Week Outside Of The Body
A team of researchers from the University Hospital Zurich and the University of Zurich have developed a machine, which can repair an injured human liver and keeps it alive for one week outside the body. The system uses perfusion technology, imitating core body functions. During the study for safety and efficacy, the team found that six of ten poor-quality human livers, originally declined for transplantation were recovered to full function within one week of perfusion on the machine. This machine proves to be a breakthrough in transplantation medicine, increasing the number of available organs for transplantation and saving the lives of patients.
Dr. Janjigian On Data With Atezolizumab/Bevacizumab Combo In HCC
Yelena Y. Janjigian, MD, a medical oncologist at Memorial Sloan Kettering Cancer Center presents results from the ongoing phase III IMbrave150 trial at the 2019 ESMO Asia Congress. The study shows improvement in efficacy and toxicity with patients with Hepatocellular Carcinoma (HCC) who are treated with bevacizumab (Avastin) and atezolizumab (Tecentriq) when compared with sorafenib (Nexavar). Grade 3/4 adverse events were more common in the combination arm (57%) versus the sorafenib arm (55%).
New Investigation Into PD-1 Blockade For Hepatocellular Carcinoma
A team of investigators are trying to determine why immunotherapy only works in select patients with Hepatocellular Carcinoma (HCC). The team is led by Thomas Marron, MD, PhD, assistant director of early-phase and immunotherapy trials at The Tisch Cancer Institute at Mount Sinai, New York, New York. Marron and his team are conducting a phase 1 clinical trial to assess the clinical efficacy and response of patients with HCC to cemiplimab therapy. Their research will include the evaluation of the therapeutic effects of the programmed death receptor 1 (PD-1) antibody (cemiplimab-rwlc), which was developed by Regeneron Pharmaceuticals, Inc, and Sanofi.
Hope Persists As Treatment Landscape For HCC Expands Dramatically
Patients with Hepatocellular Carcinoma (HCC) now have 6 FDA approved treatment options for the second-line setting, with 4 targeted therapies and 2 immunotherapies. Results of the phase III CheckMate 459 trial demonstrated an improvement in overall survival (OS) with nivolumab (Opdivo) when compared with sorafenib (Nexavar). The phase III IMbrave150 trial demonstrated improved progression-free survival(PFS) and OS with the combination of atezolizumab (Tecentriq) plus bevacizumab (Avastin) as compared with sorafenib. Also, in July of 2019, the FDA granted a breakthrough therapy designation to the combination of pembrolizumab (Keytruda) plus lenvatinib (Lenvima).
Innovent Biologics, Inc. and Sirnaomics Inc., biopharmaceutical companies, have begun a collaboration to conduct clinical studies, using Innovent's antibody drug Tyvyt® (sintilimab injection) and Sirnaomics' RNAi drug candidate STP705 (cotsiranib), for combination treatment in advanced cancers Hepatocellular Carcinomas (HCC). Patrick Lu, PhD, President and CEO of Sirnaomics, stated, "This collaborative effort between Sirnaomics and Innovent will be the first example of a combination strategy using an RNAi drug candidate together with an approved immune checkpoint antibody drug for the treatment of liver cancers.”
The principal investigator of the Phase II liver cancer study, Dr. Solomon Stemmer, of the biotechnology company Can-Fite BioPharma Ltd., will deliver a presentation titled “The Safety and Efficacy of Namodenoson in the Second-Line Treatment of Advanced Hepatocellular Carcinoma (HCC). Namodenoson is being evaluated as a second-line treatment for HCC with plans for a Phase III trial. Namodenoson is a small orally bioavailable drug that binds with high affinity and selectivity to the A3 adenosine receptor (A3AR). Results from the completed Phase II liver cancer study found that Namodenoson increased overall survival in HCC patients.CStone Pharmaceuticals And Blueprint Medicines Initiate Phase 1b/2 Clinical Trial Of Fisogatinib In Combination With CS1001 For Patients With Hepatocellular Carcinoma
CStone Pharmaceuticals, a biopharmaceutical company, has begun its Phase 1b/2 trial evaluating fisogatinib in combination with CS1001 for the treatment Hepatocellular Carcinoma (HCC). Fisogatinib, discovered by Blueprint Medicines, is a potent and highly selective inhibitor of fibroblast growth factor receptor 4 (FGFR4). CS1001 is an anti-PD-L1 monoclonal antibody being developed by CStone. The trial will assess the potential for two complementary treatment approaches, precision therapy and immuno-oncology therapy, to increase anti-tumor activity. From the ongoing Phase 1 trial showed that fisogatinib monotherapy was clinically active and well-tolerated in patients with heavily pretreated advanced HCC. These results support fisogatinib's potential as the first molecular biomarker-driven targeted therapy in HCC.
New Data From Hadassah Medical Center Lab Show Can-Fite’s Namodenoson Induces Weight Loss
According to Dr. Rifaat Safadi, head of the Liver Unit, Gastroenterology and Liver Diseases, Division of Medicine at the Hadassah Medical Center, Namodenoson induces weight loss in experimental models and normalizes glucose levels. Can-Fite's liver cancer drug, Namodenoson, recently completed a Phase II trial for Hepatocellular Carcinoma (HCC). New studies of Namodenoson showed a significant decrease in weight in both high-fat diet mouse models and in diabetic rat models. Namodenoson also normalized glucose levels in a glucose tolerance test (GTT).
Study Underway To Evaluate Novel T-Cell Therapy For Hepatocellular Carcinoma
There is currently a clinical trial in progress to assess the use of a new T-cell therapy for the treatment of advanced Hepatocellular Carcinoma (HCC). Daneng Li, MD, medical oncologist at City of Hope, said in a press release, “This approach engineers immune cells to directly attack a protein that is expressed in liver cancer. We are trying to individualize treatment for patients with advanced liver cancer.” Patients with HCC often overexpress AFP, a protein that is potentially an attractive target for HCC treatment. ET140202 ARTEMIS, by Eureka Therapeutics, is an engineered T-cell therapy for advanced HCC whereby autologous T cells are genetically modified to target the AFP-peptide and major histocompatibility complex.
First-In-World Procedure For Liver Cancer Restores Hope For Patients
Often cancer cannot be treated because of either a biological or technical reason. There are many treatment options to treat locally advanced liver cancer, including ExVivo and ALPPS. Ex Vivo involves extracting the entire liver, clearing it of cancer, and transplanting it back into the patient. ALPPS is a technique in which the portion of the liver containing cancer is removed, and the healthy portion is left to regenerate. Researchers are working to combine the procedures. Ex Vivo-APLPS procedure requires a team of 25 professionals. First, the ALPPS procedure is performed and then a period of waiting to allow the healthy liver to grow to an acceptable size. Then the Ex Vivo component is done, which involves taking the entire liver out, removing the tumor and the afflicted vessels, and reconnecting residual blood vessels, in the form of an auto-transplantation.