2016 Liver Cancer News
Reovirus Could Lead to Immunotherapy for Liver Diseases
The virus that causes coughs and colds, reovirus, could potentially be used as an immunotherapy treatment for liver diseases, such as hepatitis C virus (HCV) and primary liver cancer, a recent study found. The reovirus affects the respiratory system and causes upset stomachs in children, but the virus does not have these effects on adults, since they have typically been exposed to it earlier in life. Researchers found that this virus increases an immune system response that can kill cancer cells in the liver. These findings are significant since liver cancer is the third leading cause of cancer-related deaths around the world, and treatment options are limited if surgical intervention is not possible, according to the study published by Gut.
Study Results Show Multidisciplinary Tumor Boards Lead to Improved OS for HCC Patients
Multidisciplinary tumor boards led to higher utilization of guideline-recommended curative therapies, which was associated with improved overall survival (OS) for patients with early-stage Hepatocellular Carcinoma (HCC), according to an observational study conducted by the Veterans Outcomes and Cost Associated with Liver Disease. "Significant variability was noted for care delivery in HCC in a diverse, national cohort of Veterans," said lead investigator Marina Serper, MD, MS, Division of Gastroenterology and Hepatology, Hospital of the University of Pennsylvania. "Studies to improve multidisciplinary approaches for HCC in the community are needed to increase rates of curative therapy and improve clinical outcomes."
One more piece in the puzzle of liver cancer identified
Researchers discover unexpected role of signaling protein in Hepatocellular CarcinomaThe most common type of liver cancer, called Hepatocellular Carcinoma (HCC), is one of the most prevalent tumors worldwide. The survival rate of patients with HCC is, to date, very poor. This is in part due to the heterogeneity of the disease. HCC tumors can exhibit very different molecular features, and this poses a problem for the development of targeted therapies. Therefore, the identification of each individual piece in this molecular puzzle is vital to shed light on the entire picture of HCC, and will hopefully contribute to improve therapies in the future.
Researchers identify new suppressor effects of the NOX4 protein in liver cancer
Researchers of the TGF-beta and Cancer group of Bellvitge Biomedical Research Institute (IDIBELL), in collaboration with King's College London, have unveiled the role of NADPH oxidase NOX4 as an inhibitor of the epithelial-amoeboid transition, a process that contributes to the migration and invasion of tumor cells. The study has just been published in the journal Oncogene.
New Model for Predicting Tumor Recurrence Could Benefit Liver Transplant Patients
A simple blood test may better predict which patients diagnosed with liver cancer will experience disease reoccurrence, according to new research from Weill Cornell Medicine scientists. The findings may help physicians determine who would benefit most from liver transplantation.
Mutational Complexity Reflects Treatment Challenges for Hepatocellular Carcinoma
The growing incidence of primary liver cancer in the United States poses a great therapeutic challenge. Despite the plethora of new treatment options that have been tested, only a single targeted therapy is approved by the FDA for the treatment of the majority of patients who present with advanced-stage disease. Consequently, survival rates remain comparatively low.
HCV patients with diabetes may have increased risk of Hepatocellular Carcinoma
For hepatitis C virus (HCV)-infected patients, diabetes mellitus (DM) is associated with increased risk of Hepatocellular Carcinoma (HCC) development and all-cause mortality, according to a study published in the Journal of Gastroenterology and Hepatology.
Purdue University Research Group Links HBV Infection with Poor Liver Cancer Prognosis
Liver cancer has the fastest growing mortality rate in the United States. One major contributing factor to liver cancer progression is infection with the hepatitis B virus (HBV). Although an HBV vaccine exists, it has not been successful in eradicating HBV infection. According to the researchers on the study, the World Health Organization (WHO) estimates that over 250 million people are living with a chronic HBV infection.
He wants to bring hope to liver cancer patients
It can get scary when liver cancer recurs. But patients should not lose hope as research in this field is developing, said National Cancer Centre Singapore's senior consultant surgical oncologist, Professor Pierce Chow. He gave the example of a cancer survivor whose cancer recurred at least three times over seven years. "Each time it returned, doctors were able to treat it because medical advances allowed him to get new and better treatment," said Prof Chow who added that the man, who was first diagnosed in his 40s, is alive and doing well today.
Nanobiotix reports 'excellent' results from early stage liver cancer trial
Cancer treatment group Nanobiotix has reported ‘excellent’ results from an early stage trial of its nanoparticle technology in liver cancer sufferers. The aim with trial with NBTXR3, one of seven Nanobiotix has ongoing in various types of cancer, is to amplify the energy dose within the tumor in the liver to improve the result from treatment.
The doctor at MD Anderson Cancer Center had told Randy Smith to get his affairs in order: The cancer in his liver was too pervasive, Smith recalls him saying. He probably wouldn't survive much longer than a year. That night he lay awake in bed and prayed: "God, I'm ready to die," he remembers thinking, "but my wife and son are not ready to handle life without me. I want to live." A year later, in August, his prayer was answered. Smith, 65, received a transplant at Houston Methodist Hospital as part of a nationwide clinical trial. The replacement liver didn't come to Smith packed in ice, as typical, but instead inside a new machine that keeps the liver warm and pumping with oxygenated blood and antibiotics during transport, cleansing it of toxins and possibly making a marginal, fatty liver safe for transplant.
Unexpected Activity of Two Enzymes Helps Explain Why Liver Cancer Drugs Fail
Some cancers are caused by loss of enzymes that should keep cell growth in check. On the other side, some are caused by over-activation of enzymes that enhance cell growth. Yet drugs that inhibit the overactive enzymes have failed to work against liver cancer. In mouse models, researchers at University of California San Diego School of Medicine have discovered a potential reason — counterintuitively, lack of both types of these enzymes can lead to liver disease and cancer. In human liver tumor samples, they also found that deficiencies in these two enzymes, called Shp2 and Pten, are associated with poor prognosis.
Regorafenib Demonstrates Survival Benefit in Second-Line Setting for Advanced HCC
Regorafenib (Stivarga) demonstrates the first survival benefit in second-line setting for patients with Hepatocellular Carcinoma (HCC) who have progressed on sorafenib, according to results of the phase III RESORCE trial published in The Lancet. “Regorafenib has the potential to become the new standard or care for patients with Hepatocellular Carcinoma who progress on sorafenib,” lead author Jordi Bruix, MD said when presenting the data at the 2016 ESMO Annual Congress.
CureVac AG today announced that a study with its RNAdjuvant® technology was published in the peer-reviewed journal Cancer Immunology, Immunotherapy. The study, titled "Immunological effects of a novel RNA-based adjuvant in liver cancer patients," by Circelli et al., demonstrated for the first time ever that the company's RNAdjuvant® to be used in a therapeutic cancer vaccine formulation is equally effective on peripheral blood mononuclear cells (PBMCs) from both healthy and Hepatocellular Carcinoma (HCC) patients. The data were collected in connection with the HEPAVAC project, which is sponsored by the EU.
Canada First to Receive New Treatment Option for Liver Cancer Patients
DC Bead LUMI™ Radiopaque Drug-Eluting Bead Offers Interventional Radiologists in Canada a Next Generation Treatment Option for Liver Cancer PatientsBTG International Canada Inc. announced the commercial launch of DC Bead LUMI™ in Canada. Today's launch represents the first market commercialization of DC Bead LUMI™ in the world, with regulatory clearances and launches planned for additional markets worldwide. DC Bead LUMI™ is the first available radiopaque embolic drug-eluting bead that can be loaded with doxorubicin for the treatment of Hepatocellular Carcinoma (HCC), the most common type of primary liver cancer.
Hepatocellular Carcinoma (HCC) is also known as malignant hepatoma. HCC is the major malignancy of the liver and is found to occur mainly in patients with chronic liver diseases and cirrhosis. The cells of origin of HCC are the hepatic stem cells, although this remains the subject of investigation. The hepatic tumors proliferate with local expansion, spreading in intrahepatic region and finally distant metastases. HCC is currently expected to be the third leading cause of death worldwide.
Nanotechnology a 'green' approach to treating liver cancer
According to the American Cancer Society, more than 700,000 new cases of liver cancer are diagnosed worldwide each year. Currently, the only cure for the disease is to surgically remove the cancerous part of the liver or transplant the entire organ. However, an international study led by University of Missouri School of Medicine researchers has proven that a new minimally invasive approach targets and destroys precancerous tumor cells in the livers of mice and in vitro human cells.
Celsion Corporation announced the presentation of results from an independent retrospective analysis conducted by the National Institutes of Health (NIH) on the intent-to-treat population of the Company’s HEAT Study, a 701-patient study of ThermoDox®, Celsion's proprietary heat-activated liposomal encapsulation of doxorubicin in combination with radiofrequency ablation (RFA) in primary liver cancer, also known as Hepatocellular Carcinoma (HCC). The NIH analysis concluded that increased burn time per tumor volume significantly improved overall survival (OS) in patients with solitary lesions treated with RFA + ThermoDox® compared to patients treated with RFA alone.
Blueprint Medicines Corporation, a leader in discovering and developing targeted kinase medicines for patients with genomically defined diseases announced data from its ongoing Phase 1 trial evaluating BLU-554, an investigational medicine for the treatment of advanced Hepatocellular Carcinoma (HCC). Blueprint Medicines is developing BLU-554 as a potent, highly selective inhibitor of fibroblast growth factor receptor 4 (FGFR4). "We desperately need new treatment options for patients with liver cancer, the second leading cause of cancer deaths worldwide," said Richard Kim, M.D., Moffitt Cancer Center, an investigator for the study.
Jet lag may up liver cancer risk
Repeated jet lags may increase obesity-related liver disease as well as risk of liver cancer, a new study has warned. When we are exposed to light, our body's central circadian clock in the brain resets. By changing the times the lights went on and off during the night each week, the researchers modelled the effects of chronic jet lag in normal mice that were fed a healthy diet. They found that the mice gained weight and fat, and developed fatty liver disease, which progressed to chronic inflammation and eventually liver cancer in some cases.
Broccoli may offer protection against liver cancer
Consumption of broccoli has increased in the United States over the last few decades as scientists have reported that eating the vegetable 3-5 times per week can lower the risk of many types of cancer including breast, prostate, and colon cancers. A new study from the University of Illinois reports that including broccoli in the diet may also protect against liver cancer. “The normal story about broccoli and health is that it can protect against a number of different cancers. But nobody had looked at liver cancer,” says Elizabeth Jeffery, a U of I emeritus professor of nutrition.
FDA Grants 510(k) Clearance to New Ultrasound Modes for Liver, Breast Imaging
Aixplorer (SuperSonic Imagine) is an ultrasound system that uses an Ultrafast (SuperSonic Imagine) platform that takes images 200 times faster than other ultrasound systems. Aixplorer allows surgeons to view the liver anatomy in real time, which makes it easier to detect liver stiffness and fibrosis. “These new imaging modes provide unique information for the clinical management of patients with breast and liver disease,” Jacques Souquet, founder and chief innovation officer at SuperSonic Imagine, said in the release. “In particular, this new release will position SuperSonic Imagine as a leading innovator in the field of chronic liver diseases management and cover the whole spectrum of liver diseases from [nonalcoholic fatty liver disease] to [Hepatocellular Carcinoma].”
Do Cancer Clinical Trials Exaggerate the Real-World Benefits of Drugs?
The point of cancer trials is to determine if a drug is safe and effective to be sold to an American patient. The problem is that cancer trial participants are unlike cancer patients in the general population: they’re younger, healthier, more affluent and more able to take advantage of what the healthcare system has to offer. University of North Carolina researchers did a study in 2016 that compared results from the 2007 clinical trial for sorafenib in the treatment for HCC, to what’s happened since. In the trial, patients on sorafenib lived a median 10.7 months compared to 7.9 months on placebo. What’s interesting was that the 2.8 months difference, while not unusual for such molecularly targeted cancer drugs, was a big deal relative to patients receiving a placebo. When the researchers “…examined a cancer database run by the National Institutes of Health to see how people with liver cancer fared on sorafenib in real-world use, the results were sobering. The roughly 400 patients who received sorafenib were sicker and five years older (70 vs. 65), on average, than those in the clinical trial. And their median survival was three months — well short of the 10.7 months in the trial. In comparable patients who did not get sorafenib, but only supportive care, median survival was also three months. So there was no benefit from taking the drug.” The researchers concluded that sorafenib was not an isolated case.
Liver Cancer: Virus That Can Cause Coughs in Children Could Treat DEADLY Disease
Reovirus, which can cause respiratory illness and stomach upset in children, has been shown to fight liver cancer cells grown in the laboratory, as well as cells taken from patients during surgery. Reovirus stimulates interferon, which activates a certain white blood cell, called a natural killer cell, which then goes after liver cancer cells and the hepatitis C virus. Professor Alan Melcher, co-author of the Institute of Cancer Research, London, said, “Our study establishes a completely new type of viral immunotherapy for the most common primary liver cancer type, Hepatocellular Carcinoma, which has a very poor prognosis in its advanced form.”
Catching Them Early: Outreach Program Could Avert HCC in Cirrhosis Patients
Only 25% of patients with cirrhosis of the liver get the recommended bi-annual ultrasound screening for HCC. A recent study mailed patients with cirrhosis invitations to have the screening done and doubled the percentage of patients diagnosed with HCC. Study authors conclude that screening for HCC is underused and that more aggressive education and outreach could improve early detection of the disease.
Combination Therapy Effectively Treats Hepatocellular Carcinoma in Mice {Preclinical}
Transarterial chemoembolization (TACE) starves HCC cells of oxygen and key nutrients for survival, but does not always finish the job. Researchers combined TACE with the drug TPZ, a hypoxia-activated cytotoxic agent, in an HCC mouse model study and observed near complete necrosis of tumor cells with very little effect on surrounding tissue. Months after the combined treatment, MRIs of the mouse livers showed a complete absence of tumor cells. TACE combined with TPZ kills more HCC cells in mice than any current treatment used, but researchers caution that more testing needs to be done before human studies can commence.
Herbal Compound Promises Cure for Liver Cancer
Researchers at the Rajiv Gandhi Centre for Biotechnology at Government Medical College in Pune, India, have found that a compound extracted from the leaves of Solanum nigrum (Black Nightshade) is effective against Hepatocellular Carcinoma. The compound showed great success in suppressing tumor cells in mice and did not cause any noticeable side effects. “According to Ruby John Anto, cancer researcher at the RGCB and a lead author of the paper, various plant species of the Solanum family have been reported to have considerable amount of saponins which exhibit potent activity against different cancer cell lines.”
Italian researchers found that HCV patients cured of the disease with direct-acting antivirals (DAAs) had a slightly lower risk of developing HCC, but that those who did develop the disease had a more aggressive type. Possible reasons could be changes to the immune system due to HCV treatment. “Speaking at a press conference, Alfredo Alberti, Professor of gastroenterology at the University of Padova said that changes in the immunological and tumor-suppressive environment in the liver as a result of the rapid elimination of viral replication might permit more rapid growth of tumors already present in the liver.”
Due to the success of antivirals in treating HBV in recent years, there has been a plateau in the number of chronic HBV patients requesting liver transplantation. However, a recent study showed that the level of HCC in these same patients is still rising and investigators don’t know why. “Future studies focusing on developing better prediction models for disease progression and development of Hepatocellular Carcinoma may help better risk stratify HBV patients into more aggressive treatment and liver cancer screening and surveillance programs,” stated Dr. Robert Wong, MD., assistant clinical professor of medicine at Alameda Health System, Highland Hospital. “In addition, with the many potential HBV therapies on the horizon, it will be interesting to understand what treatment endpoints are most effective at reducing HBV disease progression and Hepatocellular Carcinoma (e.g. viral suppression, normalization of alanine aminotransferases and HBV surface antigen loss)."
Bayer Seeks FDA Approval For Regorafenib As Liver Cancer Treatment
The German pharmaceutical company’s drug to treat unresectable Hepatocellular Carcinoma, Stivarga, was already approved for Fast Track designation by the FDA. The company will now seek the government body’s approval of the drug as a second-line treatment for HCC after it showed overall survival benefit in patients taking part in the RESORCE study. It is believed that HCC patients who benefit from first-line treatment sorafenib could benefit greatly from Stivarga (regorafenib) as a second line treatment.
TACE Plus Radiotherapy Improves Survival for HCC, Portal Vein Tumor Thrombosis
Researchers analyzed data from 122 patients with unresectable HCC and PVTT who were treated with TACE combined with radiotherapy and 735 patients undergoing TACE alone. For combined therapy versus TACE alone, median survival was 11 months vs. 4.8 months respectively; median survival time was 10.9 months vs. 4.1 months, respectively. “TACE combined with RT has become an option for the non-surgical treatment of HCC with PVTT,” the researchers concluded. “Our study shows that combination therapy yields a more promising outcome in patients with HCC and PVTT, especially in patients with PVTT involving the right/left portal vein or main trunk.”
New Treatment Can Halt Growth of Liver Cancer Cells, Research Shows
In its normal state, the Arid1b gene safeguards against cancer by limiting cell growth, but when it mutates it can cause liver cancer. Two existing drugs already used to treat other forms of cancer, gemcitabine and DON, can be used the halt the growth caused by the gene mutation. Arid1b gene is part of DNA regulation in healthy cells that produces an enzyme that breaks down the building blocks of tumor cells. If Arid1b is mutated, it cannot stop cancer cell growth so the tumor grows out of control.
MIV-818 is an oral chemotherapeutic that compromises the proliferation of liver cancer cell lines. MIV-818 has been designated a candidate drug (CD) and has entered non-clinical development with preclinical results to be presented in 2017. “Many treatments that were successful in other cancers have failed to provide benefits to liver cancer patients, often because systemic toxicity prevents effective drug concentrations from being reached at the tumor site. We have designed MIV-818 to be liver-directed in order to overcome these limitations, and we look forward to advancing it into clinical trials as rapidly as possible,” said Richard Bethell, Chief Scientific Officer, Medivir AB.
The Complexities of Hepatocellular Carcinoma
VIDEO Dr. Arndt Vogel, MD and Dr. Richard Finn, MD., discuss recent discoveries in the molecular biology of HCC and how that shapes treatment for the individual patient.
October is National Liver Cancer Awareness Month and Bel Marra Health magazine has put together their top liver-related stories, which include topics like obesity, NAFLD, diabetes, liver fibrosis, hepatitis C, and liver cirrhosis.
Hepatocellular Carcinoma HCC Treatment Market 2016 – 2026 Shares, Trend and Growth Report
The global HCC treatment and market trend forecast.
Advanced HCC Prevalent in Blacks vs. Non-Hispanic Whites
An analysis of data from the Alameda Health System, Highland Hospital in Oakland, found that African-Americans with HCC were nearly four times more likely to have metastatic disease than non-white Hispanics. “While HCC incidence in the U.S. appears to have stabilized, overall survival from HCC remains to be poor,” Jonathan Chan, MD, of the Alameda Health System, Highland Hospital, said during his presentation in a liver plenary. “Racial and ethnic disparities of HCC incidence reflect differences … including ideology of liver disease. Racial and ethnic disparities of HCC survival are also affected by stage of HCC diagnosis, which affects treatment options. To evaluate [these] disparities in HCC tumor stage, diagnosis was the aim of this study at a safety-net hospital population.”
Blue Faery Asks Primary Liver Cancer Patients to Share Their Experiences in New Global Survey
Blue Faery: The Adrienne Wilson Liver Cancer Association, in partnership with other liver organizations around the world, is asking primary liver cancer patients to participate in the first international survey of people who live with HCC. The goal of the survey is to provide cancer researchers and doctors perspective and feedback that could help them develop treatments. "We understand each patient's personal fight against liver cancer is their first priority. However, each patient is also one among tens of thousands of people who are fighting a similar battle every day, in every country of the world. We believe by sharing their stories, HCC patients help decrease the stigma of a liver cancer diagnosis," said Blue Faery President and Founder Andrea Wilson.
Can-Fite Signs Distribution Deal for Liver Cancer Drug CF102 in South Korea
CF102 is a small, orally bioavailable drug that has demonstrated a strong anti-tumor effect and apoptosis in liver cancer cells. The deal coincides with the near full enrollment of CF102 in a phase II trial as a second-line treatment for HCC in South Korea. “The pressing need for an effective drug in this difficult to treat cancer makes CF102, in our opinion, a strong potential candidate as we look towards Phase II results and ahead to Phase III in the U.S. where CF102 has Fast Track Designation in this indication," stated Can-Fite CEO Dr. Pnina Fishman.
FDA Grants Orphan Drug Status to Novel Hepatocellular Carcinoma Tx
The designation is for YS-ON-001, a new treatment implementing immunomodulating cell technology. The drug exhibited strong anti-tumor benefits against breast, liver and other cancers as compared to first-line chemotherapies or targeted therapies.
Dr. El-Khoueiry on Evolving Role of Immunotherapy in HCC
VIDEO Anthony B. El-Khoueiry, MD, associate professor of Clinical Medicine, USC Norris Comprehensive Cancer Center, discusses the role that immunotherapy currently plays, and will continue to play, in the treatment landscape of Hepatocellular Carcinoma (HCC).
PharmaEngine Announces Initiation of Phase 1b/2 Trial of PEP503 (NBTXR3) in Head and Neck Cancer
PEP503, a nanoparticle formulation of hafnium oxide crystals for local tumor treatment and enhancement of radiotherapy, is in a phase 1 /2 clinical trial for liver metastasis and Hepatocellular Carcinoma in Europe.
The Ceramide Liposome delivers the drug using NanoJackets, calcium phosphate nanoparticles that can be designed to zero in on specific cell types. Data from in vivo and in vitro tests showed that Ceramides kills cancer cells while leaving surrounding, normal cells unharmed. "We are pleased to be granted orphan drug status as this helps Keystone Nano accelerate the development of Ceramide NanoLiposome (KN-001) for the patients battling Liver Cancer," remarked Jeff Davidson, Keystone's Chief Executive Officer.
Grant Awarded to Study Bavituximab, Other Therapies’ Impact on HCC
The grant will be used to launch a phase I trial to study the immunotherapy bavituximab and other therapies on patients with HCC. The researchers aim to combine several immunotherapies with stereotactic body radiotherapy to improve patients overall survival and disease response. We look forward to integrating the valuable clinical data generated by these investigators to expand our knowledge regarding bavituximab-focused cancer treatment combinations,” Joseph Shan, MPH, vice president, clinical and regulatory affairs, Peregrine Pharmaceuticals, said in the press release.
Minimally Invasive Surgery A Safe Option for Major Liver Cases, UW Study Finds
Most liver cancer patients who require surgery are only given the option of an open-abdominal procedure, but a University of Washington study suggests that minimally invasive surgery may be a better option. Minimally invasive procedures halved serious complications or death in major hepatectomies and reduce the risk of liver failure. Patients should consult with their surgeon. “It’s still up to the patient and the surgeon what the right approach is,” Dr. Lucas Thornblade, UW Medicine general-surgery resident, said.
More Evidence Links Obesity To A Certain Type of Cancer
A study conducted by the American Cancer Society found that people with a large waistline, a high body mass index (BMI), and Type 2 diabetes are at a greater risk of getting liver cancer. People with Type 2 diabetes were 2.6 times more likely to be diagnosed with liver cancer and there is an 8% higher risk of the disease for every additional two inches to the waistline. “This adds substantial support to liver cancer being on the list of obesity-associated cancers,” Peter Campbell, strategic director of digestive system cancer research at ACS, said in a journal news release. “This is yet another reason to maintain a body weight in the ‘normal’ range for your height.”
High Rates of Overall Survival Show Benefit of SBRT in Unresectable Liver Cancer
In a phase 2 study of patients with unresectable HCC who underwent incomplete transarterial chemoembolization (TACE), stereotactic body radiotherapy (SBRT) resulted in high rates of overall survival (OS), tumor local control and grade 1 /2 gastrointestinal and hepatic toxicities. After two years, OS was 83.5% and progression-free survival (PFS) was 47.2%; after three years OS was 75.1% and PFS was 37.2%. “These findings warrant confirmation in further randomized controlled trials,” Won Il Jang, MD, Department of Radiation Oncology Korea Institute of Radiological and Medical Services, said. The current trial is listed on ClinicalTrials.gov (NCT01850667)
HBV-Related HCC Declines as HCV-Related HCC Increases in Australia
In a data linkage study, the HBV cohort of HCC cases from 2001 – 2013 stabilized and decreased, but the HCV cohort of HCC cases over the same period more than tripled. The researchers suggested that the decline in HBV-related HCC was a result of more efficacious anti-viral therapy since the early 2000s. The higher rate of HCV-related HCC was due to the standard interferon treatment having no effect on the disease. “The surveillance system we have developed, particularly with the addition of individual-level HBV and HCV treatment data will be a valuable tool for evaluation of enhanced strategies for viral hepatitis diagnosis and treatment in the future,” the researchers concluded. “It will also provide the opportunity to compare population and individual-level impacts in different settings, particularly those with mandatory HBV and HCV notification and capacity for data linkage to a range of administrative datasets.”
Research Uncovers Defender Against Cancer-Promoting Liver Damage
Scientists have discovered an important signaling protein, called p62 that helps suppress liver inflammation and scarring. Hepatic stellate cells normally store vitamin A and help with organ regeneration, but when they carry p62 they becomes a support system for liver cancer cells. Researchers also found that when p62 came into contact with vitamin D, it returned the hepatic stellate cells to their vitamin A-storing role. "Whether p62 is pro- or anti-cancer appears to depend on the cell type," explained Maria Diaz-Meco, Ph.D., of the Sanford Burnham Prebys Medical Discovery Institute. "In cancer cells, it's bad, but in surrounding cells that feed the tumor, it's good. Vitamin D and its analogs may still help prevent cancer in patients with hepatitis or fatty liver disease. At that stage, enough p62 may still be present in stellate cells for the vitamin D receptor to work."
Nanodrug Helps Treat Liver Cancer
Iranian researchers have developed a nanodrug delivery system that is three times more efficient in targeting Hepatocellular Carcinoma tumor cells than typical drug delivery systems, and 35 more effective than other freely administered medication. The system delivers encapsulated herbal medication in a nanostructured liposome with monoclonal antibody marker, a method that specifically targets HCC only. “The system would provide valuable possibilities to diagnose other carcinogenic and infectious tissues; it improves the durability of medication in the body and contributes to the efficacy of the drug smartly delivered to the cells,” said the head of the research group, Dr. Mohammad Mehdi Owji.
Dr. Bruix on the Phase III RESORCE Trial in HCC
VIDEO “Jordi Bruix, MD, head of the Barcelona Clinic Liver Cancer at University of Barcelona, discusses the results of the phase III RESORCE trial in Hepatocellular Carcinoma (HCC) during an interview at the 2016 ESMO Congress.
Nivolumab May Be Better Than BSC for Advanced Hepatocellular Carcinoma
HCC patients, who receive no benefit from first-line treatment sorafenib, typically received best supportive care (BSC), with median overall survival of only 7-8 months. Results from a phase 1-2 study of nivolumab, a PD-1 inhibitor, as a second-line treatment in patients with advanced Hepatocellular Carcinoma resulted in a median overall survival in patients of 14.3 months. “In the dose expansion phase, the 6- and 9-month overall survival rates were 82.5% and 70.8%, respectively. Rates were similar between sorafenib-naive/intolerant patients and those who failed sorafenib.”
UPDATED: Bayer Counts on Nexavar-Stivarga “Continuum” to Protect It’s Liver Cancer Lead
The company announced that in a Phase III trial, Stivarga (regorafenib) reduced the risk of death by 37% in HCC patients whose disease had progressed after taking Nexavar. Overall survival (OS) was 10.6 months versus 7.8 months with placebo, which makes Stivarga the first drug to improve OS as a second-line treatment in patients with unresectable liver cancer. “We know that there are other drugs being studied in this area, but those would be one-off approvals--front line, second line--but not necessarily this continuum approach that we could actually offer physicians as they think about the totality of treatments for the patients,” said Robert LaCaze, Bayer’s Head of Oncology.
Researchers from France and Singapore will collaborate on a meta-analysis of two randomized, controlled studies of Y-90 resin microspheres versus sorafenib. Approximately 800 patients with advanced primary liver cancer have been enrolled and first results of the analysis are expected in the first half of 2017. When talking of the HCC studies in France and Singapore, SARAH and SIRveNIB, respectively, Professor Pierce Chow, Principal Investigator of the SIRveNIB study said: “… the opportunity to combine these data in a prospective meta-analysis with the results of the French SARAH study presents a compelling scientific undertaking across a much larger patient population that will significantly increase the data available for various pre-planned statistical analyses, including overall survival. This should provide physicians who treat HCC with even greater certainty of the applicability of our results in the treatment of this increasingly common and deadly cancer."
RedHill Biopharma Initiates Mid-Stage Study with YELIVA in Liver Cancer
The company has initiated a phase II study to determine safety and efficacy of YELIVA as a second-line monotherapy for 39 patients who have experienced HCC tumor progression following first-line treatment with sorafenib. The U.S. National Cancer Institute (NCI) has awarded the Medical University of South Carolina (MUSC) $1.8 million to fund the phase II YELIVA study. The NCI grant is for five years.
10 Developments in Liver Cancer
In light of October being Liver Cancer Awareness Month, a rundown of articles discussing breakthroughs and study findings for, among other drugs and treatments: Direct-Acting Antiviral (DAA) therapy, Pexa-Vec, Nexavar, Stivarga, Dovitinib, Nintedanib and Baraclude Therapy.
ITUS Demonstrates Efficacy of Its Cchek™ Early Cancer Detection Platform With Liver Cancer
“Cchek™ is ITUS's early cancer detection technology which measures a patient's immunological response to a malignancy by detecting the presence, absence, and quantity of certain unique immune system cells that exist in and around a tumor and that enter the blood stream.” The platform has been used to detect liver cancer in patients and may become an alternative to invasive surgical procedures, like biopsies, in the near future. Cchek™ has had previous success discovering breast and lung cancer, colorectal and ovarian cancer and melanoma.
Study Finds Soda Helps Fight Cancer
Chinese researchers published results of a study where 40 liver cancer patients drank sodium bicarbonate, baking soda, dissolved in water before a procedure to restrict blood flow to the tumor. The solution appeared to assist the attack on cancer cells, although there is heated disagreement online regarding the research. “The research is valid, but preliminary,” said Chao Ming, a radiology researcher at the Second Affiliated Hospital of Zhejiang University’s School of Medicine. “Repeated tests are needed.”
MRI May Be Effective Screening Test for Hepatocellular Carcinoma
The 5-year survival rate for patients with Hepatocellular Carcinoma is 20%, which means that early diagnosis is essential. Ultrasonography (US) is recommended for at-risk patients every 6 months, but its accuracy is poor. A cohort of 423 at-risk patients agreed to be screened with both MRI and US and after three rounds, 38 patients were diagnosed with HCC. “Twenty-six were diagnosed with MRI only, 1 was diagnosed with US only, and 11 were diagnosed with both. Five patients were diagnosed with computerized tomography (CT) scan 6 months after the third screening.” The study’s authors recommend that patients at-risk for HCC should get an MRI instead of US, acknowledging that the higher cost of an MRI might make US a better choice for low-risk patients.
Alpha-Fetoprotein Levels May Predict HCC Response to Ramucirumab
The REACH (Ramucirumab Drug-Product and Best-Supported Care (BSC) Versus Placebo and BSC as 2nd-Line Treatment in Participants with HCC after 1st-Line Therapy with Sorafenib) study shows that HCC patients with an alpha-fetoprotein level of at least 400 ng/mL are likely to respond favorably to ramucirumab. In the study, 565 HCC patients were randomized to receive the drug or a placebo with analysis conducted to determine drug safety, efficacy and other factors that could affect outcome. “Overall survival was best for patients with a Child-Pugh score of 5 and AFP levels of at least 400 ng/mL. There does not appear to be any survival benefit for patients with Child-Pugh scores of 6 or greater. Researchers will investigate the efficacy of ramucirumab among patients with elevated AFP levels.”
Study Assesses Efficacy of Ramucirumab in HCC by Child-Pugh Score
The Child-Pugh score is used to determine the prognosis of chronic liver disease and cirrhosis and is based on five clinical features of liver health. In the phase 3 REACH trial, HCC patients were treated with ramucirumab as a second-line treatment after first-line treatment with sorafenib. Researchers discovered that patients with a Child-Pugh score of 5 or 6 had a higher survival rate than those with a score of 7 or 8. Specifically, patients with a Child-Pugh score of 5 had a 39% reduced risk of death and those with a score of 6 had a 36% reduction risk. “In terms of safety, the toxicity profile of ramucirumab was deemed manageable regardless of Child-Pugh score, but patients with Child-Pugh scores of 7 and 8 reported a higher incidence of grade 3 or worse treatment-emergent adverse events in both the ramucirumab and placebo arms compared with those with Child-Pugh scores of 5 or 6.”
Dr. Finn on Recent Advances in the Treatment of Liver Cancer
“Richard S. Finn, MD., associate professor of Medicine at the UCLA David Geffen School of Medicine discusses both recent advances in the treatment of patients with liver cancer, as well as the future role that immunotherapy stands to have in this field.”
Despite Growing Evidence for SBRT, the Jury Is Still Out
A recent retrospective study of patients with inoperable, non-metastatic HCC compared 1- and 2- year freedom from local progression (FFLP) rates for stereotactic body radiation therapy (SBRT) and radiofrequency ablation (RFA). Patients treated with RFA had lower alpha-fetoprotein levels, a higher incidence of cirrhosis and extended follow-up compared to SBRT. In balance, SBRT and RFA 1- and 2-year freedom from local progression rates were 97.4% versus 83.6% and 83.8% versus 80.2%, respectively. “These results suggest that both SBRT and RFA are excellent choices for smaller tumors but that SBRT may be preferred for larger tumors,” the authors concluded. “Prospective, randomized clinical trials are needed to compare these two modalities, especially for larger tumors, although we are unaware of any such ongoing trials.”
Special T Cells That Target Solid Tumors Offer Potential Treatment for Pediatric and Adult Cancers
T cells, unique immune cells that help fight tumors and infections, have become the delivery system of specially designed tumor-targeting molecules called chimeric antigen receptors (CARs). Researchers have programmed T cells to express the tested CARs to recognize and attack tumor cells carrying a particular antigen on the tumor cell surface. Up to now, CARs have had success with cancers of the blood, but the investigators believe they could fight Hepatocellular Carcinoma. “We set out an ambitious goal to develop and optimize chimeric antigen receptors that can target several solid tumors and will ultimately be studied in patients in a Phase 1 clinical trial,” said Dr. Andras Heczey, associate professor of pediatrics at Baylor and Texas Children’s Cancer Center, senior author of the study.
4 Questions With An Expert: A Therapeutic Vaccine for Liver Cancer
The PHOCUS Trial compares the oncolytic immunotherapy Pexa-Vec in combination with sorafenib versus sorafenib alone in patients with advanced HCC who have had no prior systemic treatments. CURE Newsletter asks Dr. Ghassan Abou-Alfa, M.D., at Memorial Sloan Kettering Cancer Center, four questions about the ongoing PHOCUS trial and the research history of Pexa-Vec.
Onxeo Announces First Outcomes of Livatag® Preclinical Plan
The company announced data from two in-vivo studies of Livatag® in a preclinical setting. The first showed that when HCC tumor cells were implanted into the livers of mice, Livatag ® Transdrug exhibited a 12-fold increase in exposure in tumor tissue compared to free Livatag® with no increased exposure to the heart or other vital organs. The second study found that when Livatag® was combined with immune-oncology agents called checkpoint inhibitors, the therapy had an enhanced effect on HCC tumors.
Conflicting Evidence Surfaces on Anti-HCV Drugs for Liver Cancer
While the new generation of direct-acting antivirals (DAAs) have proved successful against the hepatitis C virus, there is some evidence that shows DAAs have promoted HCC recurrence in patients who have been cured of the disease. Spanish researchers reported that 27.6% of 58 HCC patients who were cured had HCC recurrence after going back on anti-HCV drug treatment. However, French researchers, culling data from three multicenter trials of chronic HCV or cirrhosis-related HCC patients, found a lower incidence of HCC recurrence when the patients went back on direct-acting antivirals. “We need to have more data properly analyzed with the populations fully defined,” said Jordi Bruix, MD, PhD, director of the Barcelona Clinic Liver Cancer Group (BCLC), adding that it may turn out that some patients with HCC will either not benefit from the DAA therapies or may experience adverse events.
Liver Cancer Treatment Using Surefire Technology Results in 92% Objective Response Rate
Recent data from a multi-center registry, which used the Surefire Precision Infusion System during transarterial chemoembolization (TACE) to treat HCC, reported a 68% complete tumor response and a 92% objective tumor response. The patient cohort consisted of 32 patients with 41 lesions at multiple cancer treatment centers across the US. “TACE procedures utilizing the Surefire Infusion System were shown to effectively deliver therapy to the tumor,” said Aravind Arepally, MD, Chief Scientific Officer for Surefire Medical. “The objective response rate shown in this multi-center registry is considerably higher when compared to the average response rate we see in the literature.” Surefire is also conducting a 140-patient, randomized, controlled multi-center study comparing their treatment to standard drug-eluting bead transarterial chemoembolization (DEB-TACE) and is currently enrolling new patients.
Early Signals Positive for Immunotherapy Plus Standard Therapy in HCC
In a phase I/II pilot study at the National Cancer Institute (NCI), investigators treated advanced HCC patients with tremelimumab, an immune checkpoint inhibitor, and either transarterial chemoembolization (TACE) or radiofrequency ablation (RFA). Among the 23 patients that were given the combined therapy, median time to progression of HCC was 7.4 months and median overall survival was 13.6 months. “The treatment is extremely well tolerated,” said Tim F. Greten, MD., senior investigator at NCI. Additionally, Greten: “…noted tremelimumab demonstrated disease control rates of 76.4% as monotherapy in a 21-patient study and 84.2% in combination with ablation in a 32-patient cohort. In a larger trial among 206 patients, the PD-1 inhibitor nivolumab (Opdivo) resulted in a 9% overall response rate and a decline in tumor burden for 39% of 174 evaluable participants.”
Contrast Ultrasound Identifies Deadly Liver Cancers
Contrast Enhanced Ultrasound (CEUS) uses tiny bubbles to better identify liver cancer tumors and has shown better results when MRI imaging was inconclusive. CEUS employs liquid suspensions of tiny gas microbubbles to heighten reliability and clarity of the ultrasound image without patient exposure to ionizing radiation. "The findings are extremely exciting because this study appears to represent the first time ultrasound microbubbles have been used in patients for drug delivery," according to Dr. Steven Feinstein, Co-President of ICUS and a professor of medicine at Rush University, Chicago.
Breast and Liver Cancer Drug Breakthrough: Experimental Drug Could Fight Specific Diseases
The drug pevonedistat is currently being tested to treat melanomas, but it does not kill cancer cells directly. Instead, it focuses on proteins that cancer cells need to replicate and develop. Pevonedistat blocks the critical protein CDT2 that prevents cancer cells from replicating and researchers have suggested that it could be effective in treating Hepatocellular Carcinoma
twoXAR Sets Sights on Liver Cancer With New Collaboration
twoXAR, a company that uses computation to improve health, will collaborate with Stanford University School of Medicine to focus on finding drug candidates to treat Hepatocellular Carcinoma. Viable drugs will be tested in preclinical studies at the Asian Liver Center at Stanford University under the leadership of Mei-Sze, PhD. Senior Scientist at the lab of Samuel So, MD. “New drugs in development for HCC primarily target tyrosine kinases, but they have demonstrated mixed success in clinical trials, suggesting a need for new therapies targeting a more diverse set of biomarkers,” said Andrew A. Radin, co-founder and CEO of twoXAR. “We are very pleased to be working with Dr. So and his colleagues at the Asian Liver Center who are dedicated to improving outcomes for patients and raising awareness of chronic hepatitis B infection and its connection to liver cancer.”
The National Comprehensive Cancer Network (NCCN) has awarded Jessica Frakes, MD., a grant to study the effects of bavituximab and combination therapies to fight Hepatocellular Carcinoma. The study, “A Phase I Trial of Sorafenib and Bavituximab Plus Stereotactic Body Radiation Therapy (SBRT) for Unresectable Hepatitis C Associated Hepatocellular Carcinoma,” will take place at Moffitt Cancer Center. Bavituximab is an investigational immunotherapy engineered to help the body’s immune system target and diminish the function of highly immune-suppressive signaling molecules on the surface of HCC cells.
CELESTIAL is a randomized, placebo-controlled, double-blind study of the effects of cabozantinib in 760 patients with advanced HCC around the world. Following interim analysis, which occurs when 50% of events necessary for primary endpoint of survival have occurred, the Independent Data Monitoring Committee (IDMC) announced that the study should continue without changes to protocol. When 75% of events have occurred, a second interim analysis will take place. “The primary endpoint for the trial is OS, and secondary endpoints include objective response rate and progression-free survival. Exploratory endpoints include patient-reported outcomes, biomarkers and safety.”
US Veterans Have Increased Frequency of HCC at Autopsy
A single-institution autopsy study of 405 male veterans from 2005 – 2014 confirmed data from a previous study that found veterans have a 2.5-fold increase in the incidence of HCC compared to the general population. For metastatic tumors, the average age at diagnosis was 66.3 years and for primary HCC 69.5 years with chronic hepatitis C and cirrhosis as significant risk factors. The researchers also found that veterans have a 2.5-fold lifetime likelihood of alcoholism versus the general population.
Australian Risk for HBV-Related HCC declined, HCV-HCC Risk Increased
The individual risk for HBV-related HCC in New South Wales, Australia has decreased between 2000-2014 while the risk for the general population has stayed the same, a new study has found. Over the same period, the general population’s risk for HCV-related HCC has risen while the individual risk remained unchanged. The research suggests that the HBV antiviral therapy introduced in the mid-2000s has had an impact while the interferon-based HCV therapy has not. “The recent development of highly effective interferon-free DAA therapy, and Australian Government subsidization of several regimens from March 2016 provides the opportunity to rapidly scale-up HCV antiviral therapy and provide individual-level and population-level benefits in terms of HCC and other liver disease burden reductions,” the researchers wrote.
Regorafenib Improves Survival for Unresectable Liver Cancer
Results from the phase III RESORCE (regorafenib after sorafenib in Hepatocellular Carcinoma) sorafenib trial as a second-line treatment showed a 38% reduction in risk of death. Overall survival for 379 patients taking regorafenib was 10.6 months versus 7.8 months for 194 patients taking a placebo. Jean-Luc Raoul, MD, Team Leader for Translational Medicine in Digestive Cancers, Institute Paoli-Calmettes, Marseille, France, noted that previous trials of known first-line drugs (sunitinib, brivanib, linifanib, sorafenib plus erlotinib, and sorafenib plus doxorubicin) and new second-line drugs (brivanib, everolimus, ramucirumab, and ADI-PEG 20) had all failed. “Raoul declared that regorafenib is the gold standard in second-line post-sorafenib treatment in patients who tolerate sorafenib, with real and meaningful benefit in overall survival, time to progression, and overall response rate.
Researchers have determined that a group of immune cells, called tumor-infiltrating B cells (TiBs), are white blood cells that have left the bloodstream to infiltrate cancerous tissue. Depending on their type, they can either encourage or control tumor growth and research has shown that there is a correlation between the density of TiBs inside of tumors and the survival of the patient. "The close proximity of TiBs and T cells suggests a functional interaction between them that enhances local immune activation," says Alessandra Nardin of the A*STAR Singapore Immunology network. "TiBs are needed to help T cells control the growth of the tumor and slow cancer progression. We were pleased to discover that TiBs can also act as an independent indicator of improved disease prognosis."
In a retrospective study of 172 HCC patients with HCC from 2002 – 2012, albumin/globulin ration (AGR) and its association with the progression of HCC was assessed. “Pretreatment AGR might serve as an effective biomarker to evaluate the prognosis of patients with a diagnosis of HCC. Based on the results, AGR, characterized with easy accessibility, objectivity, and noninvasiveness, should be included in the routine assessment of HCC.”
Pfizer Buying Maker of Prostate-Cancer Drug Xtandi for $14B
Xtandi is a potential treatment for Hepatocellular Carcinoma, among other diseases, according to a press release after the sale.
11 Answers to Questions About Liver Cancer
According to data from “Cancer in Los Angeles County: Trends By Race/Ethnicity 1976 – 2012”, liver cancer rates for non-Asians in LA county have doubled in the last four decades. From 2005 – 2012, liver cancer rates for white men increased 33% and 21% for Latino men and while the Vietnamese are the most likely group to be diagnosed with liver cancer, during this period their incidence of the disease dropped. Data from the book shows that hepatitis C is a major cause of liver cancer for whites; chronic hepatitis B a major factor for Asians and that obesity and diabetes are major causes for Latinos.
Celsion Liver Cancer Data Underscores Company’s Potential of Its Technology
ThermoDox is the company’s heat-activated system of delivering targeted chemotherapy to liver cancer tumors. Recent data from the OPTIMA trial showed that 41% of patients saw meaningful improved survival when Thermodox was used in combination with radio-frequency ablation (RFA) versus RFA alone. “These findings, if borne out in our ongoing OPTIMA trial, will position ThermoDox as a potentially curative treatment in primary liver cancer,” stated Nicholas Borys, Celsion’s chief medical officer.
The final retrospective analysis of the 701-patient study of the company’s heat-activated liposomal encapsulation of doxorubicin combined with radio frequency ablation (RFA) showed a 54% improvement in overall survival of patients. Additionally, Thermodox® combined with RFA for 45 minutes or more optimized the treatment. “Data from the HEAT Study have consistently been a foundation and provides additional evidence for our thesis that ThermoDox®, when combined with RFA standardized to a minimum of 45 minutes for intermediate size lesions, has the potential to significantly improve survival in primary liver cancer, where the current overall survival rate is far too short,” stated Nicholas Borys, M.D., Celsion's senior vice president and chief medical officer. “These findings, if borne out in our ongoing OPTIMA trial, will position ThermoDox® as a potentially curative treatment in primary liver cancer.”
From March 2007 to March 2013, 103 patients with unresectable HCC who underwent transarterial chemoembolization (TACE) participated in a retrospective study to discover the efficacy of Jianpi Ligan decoction (JLD) as an adjuvant therapy. Of the group, 53 patients accepted JLD with TACE while the other 50 accepted TACE as their sole therapy. “Application of JLD was effective for reduction of side effects and improvement of long-term survival for patients with unresectable HCC treated by TACE.”
Hepatitis B and HIV Combo May Promote Liver Cancer
Liver cancer typically occurs in Africans aged 30 – 40, but according to a new study, those infected with HIV and hepatitis B are diagnosed at a much younger age. The study spotlights the need for better screening for the HBV to garner an earlier diagnosis to prevent liver cancer.
Hepatitis Testing and Prevention Information Offered on World Hepatitis Day
At a World Hepatitis Day event held in Los Angeles, people received free on-site testing for hepatitis B and C, HIV and sexually transmitted infections to protect themselves from viral hepatitis. While approximately 400 million people around the world are living with hepatitis B or C, only 5% know they are infected and 1.4 million people die annually, which translates to 4000 people a day. The hepatitis B virus is 100 times more infectious than HIV/AIDS and can lead to primary liver cancer, lifelong infection, cirrhosis and liver failure. “People with or at risk of viral hepatitis do not wear badges,” said Dr. Sammy Saab of the Pfleger Liver Institute at Ronald Reagan UCLA Medical Center. “Screening and early intervention [are] critical. Working together we can eradicate viral hepatitis in our lifetime.”
First Patient Treated in Phase 3 Trial for HCC Medication Pexa-Vec
Researchers have treated their first patient in the phase 3 Hepatocellular Carcinoma clinical trial of Pexa-Vec. The PHOCUS trial will enroll 600 advanced liver cancer patients and give one group Pexa-Vec followed by sorafenib and the other group sorafenib alone. The primary objective is overall survival of patients, with secondary endpoints including time to tumor progression, progression-free survival, disease control rate and overall response rate. “Having been involved in a prior clinical trial using Pexa-Vec, I remain excited about the potential this new cancer immunotherapy holds,” Laura Findeiss, MD, professor and chair of the department of radiology at the University of Tennessee Medical Center and UT Graduate School of Medicine, said in the release. “At the University of Tennessee Medical Center, we are at the forefront of bringing innovative cancer treatment to patients.”
DC Bead ® and DC Bead M1® are drug eluting loaded with chemotherapeutic agents that are delivered via embolization for local treatment of tumors in patients with HCC. The reclassification allows UK patients with HCC to be treated with the DC Bead® and DC Bead M1 ® in an approved clinical setting. "We are delighted to receive the Class III CE Mark approval for DC Bead® and DC BeadM1TM. Their ability to administer medicines in a controlled and sustained manner after chemoembolization is widely documented and their clinical use and patient benefits are supported by extensive product-specific clinical data generated by BTG and the healthcare professionals we support" commented Russell Hagan, BTG Chief Technology Officer, Interventional Oncology.
Roswell Park Cancer Institute researchers looked at the expression levels of immunosuppressive cells in advanced HCC patients and found that low levels of a “checkpoint” molecule, called PD-1, corresponded with better patients’ overall survival. Additionally, the team found that sorafenib combined with immune-based therapies might improve patient outcomes. "These results indicate that patients with an increased number of cells expressing the checkpoint molecule PD-1 before treatment are more responsive to sorafenib therapy. These increased numbers in pretreatment blood samples may be a biomarker indicating which patients will respond better to therapy and may help to predict overall patient survival," adds Dr. Yasmin Thanavala, PhD., and senior author of the paper.
Statin Use Associated With Dose-Dependent Reduction in Cirrhosis, HCC in Patients with HCV
The effectiveness of statins at reducing HCC and cirrhosis is common knowledge, but a recent Massachusetts General Hospital study shows that the preventive effects of statins is strong even in patients without sustained viral response to HCV. Additionally, the statins atorvastatin and fluvastatin are the most effective, depending on the dose. “On the choice of statin, and the potential relevance of dosing, the current study provides some hints,” Juan G. Abraldes MD, from the University of Alberta wrote. “But not definitive answers.”
Cancer-Fighting Bacteria: Engineers Program E. Coli To Destroy Tumor Cells
Certain bacteria, like E. coli, thrive in the low oxygen environment of tumors and they tend to accumulate in the liver because it’s the liver’s job to filter the bloodstream of such toxins. University of San Diego (UCSD) researchers programmed harmless strains of E. coli bacteria to deliver high-dose payloads of a traditional cancer drug to aggressive liver tumors in mice and were successful in reducing the size of those tumors. “Tumors can be friendly environments for bacteria to grow, and we’re taking advantage of that,” says Sangeeta Bhatia, who is the John and Dorothy Wilson Professor of Health Sciences and Electrical Engineering and Computer Science at MIT and a member of MIT’s Koch Institute for Integrative Cancer Research and its Institute for Medical Engineering and Science.
Theaflavins, black tea polyphenols that are plant-based molecules with anti-oxidant and anti-inflammatory properties, could substantially reduce proliferation, invasion and migration in HCC cells in vitro, according to a Chinese study. The researchers found that theaflavins not only inhibited growth and metastasis of HCC in a laboratory setting, but also found that it also induced tumor cell death, and could be a future therapeutic agent for HCC.
Lipiodol transarterial chemoembolization (TACE) is a standard treatment for unresectable, large, non-invasive isolated tumors in patients with intermediate stage HCC. The researchers performed a thorough review of published articles from 1980 – 2013 for efficacy and safety that included over 25,000 patients treated with TACE. “Based on the analysis of safety information available in literature, no new safety concerns were identified,” Riccardo Lencioni, MD, and colleagues wrote. “The most common cause of death was liver insufficiency leading to hepatic failure, which suggests that accurate patient selection, based on careful assessment of baseline liver function parameters, may be a key factor to minimize the risk of treatment-related death and reduce liver-related adverse events.”
Extended Toronto Criteria, Milan Criteria Provide Similar 10-Year Survival Rates
The Toronto and Milan criteria are used to determine whether HCC patients should receive liver transplant by determining which patients should be excluded due to poor prognosis of survival. Liver transplant offers the best chance at survival for patients with decompensated cirrhosis of the liver and Hepatocellular Carcinoma. ‘”The Milan Criteria uses tumor size and number whereas the Extended Toronto Criteria uses tumor differentiation, cancer-related symptoms, confinement to the liver and venous or biliary tumor thrombus for patients who were previously excluded from transplant by the Milan criteria.” Both criteria offered a similar rate of survival for patients.
Polaris Changes ADI-PEG 20 Approach
ADI-PEG is a treatment designed to breakdown arginine, an amino acid essential to tumor cell function and the growth of certain cancers, including Hepatocellular Carcinoma. A phase III study of ADI-PEG as a second-line treatment for HCC failed to show improved overall survival for patients. Median OS for patients receiving treatment was 7.8 months compared to 7.4 months for patients receiving a placebo. “The company said it would explore alternative roles for ADI-PEG 20, such as using the treatment as a component of combination therapy as a first-line treatment, as well as using higher dosages to promote longer arginine depletion,” said Wu Bor-wen, Polaris Group CEO.
Direct-Acting Antiviral Treatment Linked with HCC Recurrence For Patients With Hepatitis C Infection
Data from a retrospective cohort study shows that cirrhotic patients with a previous history of HCC who were treated with direct-acting antiviral (DAA) therapy had a 29% recurrence rate of the disease compared with 3.2% rate in patients with no history of HCC. Patients that are positive for hepatitis C are 15 – 20 times more likely to develop Hepatocellular Carcinoma, the second most common cancer-killer in the world. “Even in a relatively short observation period, we have shown that high recurrence rates of Hepatocellular Carcinoma can occur in hepatitis C patients taking direct-acting antivirals,” commented Dr. Federica Buonfiglioli, lead author of the study. “Even though further investigation is needed, we believe our findings justify close monitoring for all cirrhotic patients on such treatments.”
Infant HBV Vaccination Prevents HCC In Children, Young Adults
A research team out of Taiwan used a national cancer registry that identified 1509 HCC patients diagnosed from 1983 – 2011 and compared those that were born before and after the advent of the HBV vaccine. The incidence and risk of developing HCC were significantly reduced in the vaccinated group. According to the study, all individuals in the 1992 – 2005 birth cohort received the HBV vaccine and were 73% and 54% less likely to develop HCC than earlier cohorts in 1984 – 1986 and 1986 – 1992, respectively.
Regorafenib Drug Improves Survival Rates in Patients With Hepatocellular Carcinoma
The Phase III RESORCE trial enrolled 573 advanced HCC patients previously treated with sorafenib and participants were given either oral regorafenib (Stivarga) or a placebo. Patients on regorafenib showed a 34% drop in risk of death and a 54% drop in risk of death compared to placebo. Dr. Jordi Bruix, principal investigator of the study, said the safety and side effects or regorafenib were similar to sorafenib and that the drug showed efficacy regardless of stage or cause of tumor. "This is a very difficult to treat cancer but now we have an effective second-line agent, which is good news for the patients and also for the field as interest in further developments will be stimulated," Dr. Bruix said.
Global Hepatocellular Carcinoma (HCC) Pipeline Review 2016- Market Reports Center
“The report provides comprehensive information on the therapeutics under development for Hepatocellular Carcinoma, complete with analysis by stage of development, drug target, mechanism of action (MoA), route of administration (RoA) and molecule type. The report also covers the descriptive pharmacological action of the therapeutics, its complete research and development history and latest news and press releases. Additionally, the report provides an overview of key players involved in therapeutic development for Hepatocellular Carcinoma and features dormant and discontinued projects.”
Premedication With Anitemetic Improves Length of Stay and Readmissions for a Liver Cancer Procedure
Liver cancer patients undergoing drug-eluting bead chemoembolization (DEB TACE), a procedure that delivers drug-coated, chemotherapy beads directly to the liver tumor, sometimes experience post-embolization syndrome (PES). The syndrome usually occurs within the first 72 hours of the procedure and causes fever, nausea, pain and vomiting. Researchers studied 113 liver cancer patients, who underwent DEB TACE and were given dexamethasone and fosaprepitant, drugs to prevent nausea and vomiting and found that only 4.4% of patients were admitted for PES. “These findings suggest that outpatient DEB TACE could be possible with premedication and a low incidence of hospital readmission for PES,” Abouelmagd Makramalla, MD, and principal investigator of the study said. “Patients would be allowed to recover more comfortably in their homes and save time and money for both the patients and the hospital.”
Baraclude Therapy For HBV Leads To Lower Than Expected HCC Incidence
Researchers evaluated 841 HBV-infected patients in the ENUMERATE clinical study who were treated with the antiviral therapy Baraclude (entecavir) and saw a 64% lower observed than expected incidence of HCC. Over a follow-up time of eight years, researchers expected to see 30.2 cases of HCC, but observed only 17 cases. The researchers concluded: “[Entecavir] antiviral therapy was associated with a lower than expected incidence of HCC. However, the risk of HCC persisted in patients with [chronic HBV] and careful surveillance for HCC remains warranted in these patients regardless of the response to [entecavir] antiviral treatment.”
Celsion Highlights Potentially Curative Approach to Treatment of Primary Liver Cancer
An overview of the company’s lyso-thermosensitive liposomal doxorubicin (LTLD) treatment suggests that the longer the targeted tumor is heated, the greater the doxorubicin tissue concentration. Based on these findings, the paper explores a new hypothesis: LTLD used in combination with radiofrequency ablation (RFA) with a minimum dwell time of 45 minutes, may increase overall survival of HCC patients. Michael H. Tardugno, Celsion's chairman, president and chief executive officer, said in response to the article's publication. "We believe strongly that ThermoDox® (doxorubicin) may be an important new approach to the treatment of HCC. We are also now committed to learning more about how an LTLD regimen may prolong the survival of patients suffering from this extremely deadly cancer."
In a retrospective analysis of 32 HCC patients who were treated with either transarterial chemoembolization (TACE) or TACE with drug-eluting beads (DEB-TACE), survival time, disease recurrence and side effects were compared. Overall, median survival time with TACE was 10.8 months versus 9.2 months with DEB-TACE. The DEB-TACE group experienced more post-interventional pain than the TACE group.
Liver Cancer: Blocking Metabolism Starves Cancer Cells Paving Way For New Treatments
The metabolism of liver cancer cells needs glutamine, an amino acid, as fuel to proliferate. In a recent study, scientists have blocked the protein LRH-1 which helped cancer cells convert glutamine into fuel and stopped cancer cell proliferation. This discovery is important because it could lead to the development of new effective targeted drugs for liver cancer – a disease for which there is currently little treatment. "We could develop drugs that could stop the proliferation of cancer tumors by targeting LRH-1. They could be given in combination with other drugs that would kill cancerous cells once their progression has been stopped,” explained co-author Hadrien Demagny.
SIRveNIB Hepatocellular Carcinoma Study Completes Enrollment
A multi-national partnership has announced full enrollment of 360 patients in a trial to compare the efficacy of SIR-Spheres Y-90 microspheres versus sorafenib in the treatment of Hepatocellular Carcinoma. Selective internal radiation therapy (SIRT) treats inoperable liver tumors by delivering radioactive microspheres via catheter into liver arteries for a short-term radiation dose up to 40 times higher than conventional radiotherapy. For patients with advanced HCC, sorafenib is the standard treatment, but 80% of patients have treatment-related adverse effects. “The search for more effective and better tolerated treatments of HCC is important, as so few proven treatment options currently exist,” Professor Pierce Chow, MBBS, investigator on the SIRveNIB study and senior consultant surgeon at the National Cancer Centre Singapore, said in a press release. Results of the study are expected in the first half of 2017.
Adding Doxorubicin to Sorafenib Does Not Improve Overall Survival in Hepatocellular Carcinoma
A Phase 3 study sponsored by the National Cancer Institute (NCI) found that adding doxorubicin to sorafenib did not improve overall survival or progression-free survival in HCC patients, and actually increased toxicity in patients versus sorafenib as a stand-alone treatment. Median overall survival for combination treatment was 8.9 months versus 10.5 months for sorafenib as a standalone treatment. Median progression-free survival was 4 months and 3.9 months, respectively.
Blood-Borne Molecules Could Predict Those Who Will Develop Liver Cancer
Researchers analyzed the molecular signatures of blood samples from a large cohort of HBV-infected patients and found that in the patients that developed HCC, a number of microRNAs changed their normal gene expression before the patients developed cancer. MicroRNAs are small molecules that regulate gene activity, and these changes in expression could be used to predict which patients have a high likelihood of developing HCC. "This research confirms previous work on microRNAs and liver cancer and goes further to show that these microRNAs may be able to predict the development of liver cancer through a non-invasive blood test," says first author Chun Wang, a visiting scholar in the Department of Medical Oncology.
Survival For Patients With Liver Cancer Differs By Race
Researchers at the University of Miami studied 999 HCC patients between January 2005 and December 2014 and found that black patients had a 33% higher risk of death than non-Hispanic whites did. Black patients were also less likely to undergo liver transplants that would save their lives. "When we looked at a diverse sample of patients being diagnosed with HCC, race was the strongest predictor of survival," said Patricia D. Jones, MD, MSCR, assistant professor of medicine and member at Sylvester Comprehensive Cancer Center at the University of Miami Miller School of Medicine, Florida, and lead author of the study. "Black patients were more likely to present with tumors that were larger — indicating that they were at a later stage of HCC when diagnosed, potentially delaying their eligibility for a liver transplant, a curative option for HCC."
RNA Therapy Starts First-of-a-Kind Trial to Treat Liver Cancer
The field of mRNA-based therapies against cancer restores normal function to patients’ cells. Mina Therapeutic has designed a small activating RNA (saRNA), called MTL-CEBPA, which is important to normal liver function. The OUTREACH trial will determine if increasing its expression is effective in fighting liver cancer. The multi-center Phase I study will assess the safety and tolerability of MTL-CEBPA in patients with advanced primary or metastatic liver cancer who are ineligible or resistant to standard therapies.
Pexa-Vec is viral therapy designed to target and destroy cancer cells through the breakdown of cancer cell replication, the reduction of blood flow to the tumors and by stimulating the body’s immune system to fight the cancer cells. PHOCUS is a Phase 3 trial that treats HCC patients with Pexa-Vec followed by Sorafenib, as a first-line treatment. SillaJen plans to enroll 600 patients in North America, Europe and Asia who have not received prior systemic treatment for liver cancer.
Targeted Treatment for Liver Cancer Underway
Finnish researchers have found that when the function and interaction of the p53 and two other liver proteins is disturbed with a specific drug molecule, HCC cancer cells die. Following the discovery of this potential treatment, the University of Eastern Finland has embarked on the development of a new cancer drug, with the assistance of universities and research institutes in Germany and France.
Study Finds Blacks More Likely To Die From Liver Cancer
University of Miami Miller School of Medicine researchers studied almost 1000 patients diagnosed with liver cancer. They found that blacks usually had bigger tumors and the authors suggest that this was because the patients were being diagnosed later, which also made them less eligible for liver transplant. Dr. Patricia Jones, lead author, found that liver transplants led to a 66% survival rate, but that only 12% of blacks received them. Additionally, average survival for blacks after diagnosis was 301 days, compared to 437 days for Hispanics and 534 days for whites. “According to Jones, possible causes for these differences include less access to care, lower rates of health insurance and higher rates of hepatitis B, a virus that is a leading cause of liver cancer. Jones and her team did not find any evidence that the racial disparities could be attributed to racial bias—for instance, no patients were treated differently in terms of their care based on race.“
OSE Pharma and Effimune Launch Liver Cancer Study
The MDScan (Myeloid-Derived Suppressor Cell Analysis) research program is an immunotherapy designed to activate or regulate the body’s immune system to fight HCC. French biotechs OSE Pharma and Effimune are collaborating on this public-private study with MDScan being the first immunotherapy in the pipeline. Bernard Vanhove, chief executive of Effimune, said, “We are pleased to collaborate with excellent complementary academic teams to develop this novel product’s potential through a therapeutic strategy arising from our knowledge acquired in immunology of transplantation and applied in immuno-oncology.”
High Levels of Protein p62 Predict Liver Cancer Recurrence
Liver protein p62 acts as the liver cell’s trash collector, as well as a communication hub that helps in the regulation of important cellular functions like survival and growth. Because elevated p62 levels are known to be present in liver cancer and pre-cancerous liver diseases, researchers believe the protein could be used as a predictor of and potential therapeutic target for liver cancer. "Our new study illustrates that p62 is necessary and sufficient to induce liver cancer in mice, and that its high expression level in liver tissue surrounding a tumor predicts recurrence of the disease after tumors are removed," said study co-senior author Jorge Moscat, PhD., from the Cancer Center at Sanford Burnham Prebys Medical Discovery Institute. "We believe that small molecules that interfere with p62 may be useful for preventing the progression of chronic liver disease to liver cancer."
TRC105, in combination with Nexavar (sorafenib), showed a 40% response rate in a Phase II, NCI-sponsored trial for the treatment of HCC. TRACON has launched a multi-center clinical trial to explore further the safety and efficacy of the treatment. “This Phase 1b/2 study is an open-label, non-randomized clinical trial of TRC105 in combination with Nexavar in patients with HCC who have not received prior systemic therapy. TRC105 will be dosed every other week in combination with standard dose Nexavar (800 mg per day). Approximately 39 patients are expected to enroll at multiple centers in the United States and top-line data is anticipated in 2017. Additional information on the trial can be found at https://clinicaltrials.gov/, trial identifier NCT02560779.”
A group of Medicare patients with HCC was treated with sorafenib, the only FDA-approved drug for the disease, and median survival was only three 3 while median survival for patients in the clinical trial was 11 months. Researchers are questioning the value of the drug as it comes with significant side effects and a $10,000-a-month price tag. The study concluded that the lower survival rate in the Medicare population was probably due to a generally sicker population while HCC patients taking part in the clinical trial may have been treated at an earlier stage, which would improve the effectiveness of the drug. "This is obviously going to present financial challenges for many patients,” author Stacie Dusetzina, PhD., UNC Lineberger Comprehensive Cancer Center said. "This underscores the fact that establishing effectiveness of therapies outside of trial settings is complicated but important, if we want to really understand the value of cancer therapies. Translating the benefits of treatments into a 'real world' setting isn't always easy."
Vaccine Therapy for Liver Cancer Introduced in Vietnam
HEPAVAC, a vaccine for the treatment of liver cancer, has been approved by six European nations for clinical testing.
Testing a Cure for Hepatocellular Carcinoma
Lyso-thermosensitive liposomal doxorubicin (LTLD, Thermodox) is a treatment designed to be used in combination with radiofrequency ablation (RFA) for HCC tumors 3-7cm in size. When heated, LTLD provides a 25-fold greater concentration of doxorubicin than non-heated LTLD and offers three benefits to patients: ablating the visible tumor, increasing the antitumor activity of doxorubicin and generating a high doxorubicin concentration in the heated, targeted area. In addition, “...Researchers found that the amount of bioavailable doxorubicin in the tumor margin increases as RFA heating time increases from five to 60 minutes. About 89% of the total doxorubicin concentration had been achieved by 45 minutes.”
According to a study published in the journal Cancer, the median cost to treat an HCC patient with hepatitis C and cirrhosis is $175K, which equates to $6,279 per patient-month of observation. Median costs per patient-month for transplant patients was $7,492 and for non-transplant patients $4,830. “Two of the principle drivers of the cost of care for patients with chronic HCV are the complications of decompensated cirrhosis and HCC,” Elliott B. Tapper, MD, a clinical fellow in medicine at Beth Israel Deaconess Medical Center, said in a news release. “HCV therapy, therefore, presented a tradeoff. The upfront costs of viral eradication could be offset by the prevention and cost of complications in the end. Accordingly, data are needed on the true costs of HCC care to structure realistic cost-effectiveness models.”
HCC Patients Seen At High-Volume Hospitals Have Improved OS
A University of Texas study evaluated 17,231 HCC patients at 322 Texas hospitals from 2000 – 2011 and stratified high-volume hospitals as having more than 24 patients. Patients at high-volume hospitals had localized disease 56% of the time versus 50% at low-volume hospitals. Additionally, patients were more likely (22%) to have curative therapies like resection and transplantation at high-volume hospitals as opposed to low-volume hospitals (12%). “Our results support and expand on prior reports demonstrating an association between hospital volume and survival in patients with HCC,” the researchers concluded. “This benefit is particularly evident among those with localized or regional disease likely related to improved administration of HCC-directed therapy.”
Stivarga Improves Overall Survival in Hepatocellular Carcinoma Study
RESORCE (regorafenib after sorafenib in patients with Hepatocellular Carcinoma) is Bayer’s randomized, double-blind, placebo-controlled phase III trial to determine the safety and efficacy of regorafenib in 573 HCC patients. The drug has met its primary endpoint of a significant improvement in overall survival with acceptable safety and tolerability in patients.
HK Scientists Find Probiotic Mix’s Benefits in Liver Cancer Treatment5
Hong Kong scientists have developed Prohep, a probiotic mixture that was found to slow HCC tumor growth in mice significantly, which could potentially offer a much cheaper alternative to conventional HCC treatments. The researchers found that feeding mice Prohep one week before the HCC tumor was injected with conventional therapy reduced tumor weight and size by 40%. “The successful demonstration of probiotic efficacy in retarding Hepatocellular Carcinoma tumour growth in a pre-clinical model will warrant further testing of our approach in a microbiome-based intervention trial in cancer patients,” stated Dr. Hani El-Nazami of the School of Biological Sciences at the University of Hong Kong.
YELIVA ™ is in a phase II study to determine safety and efficacy as a second-line monotherapy for 39 patients who have experienced HCC tumor progression following first-line treatment with sorafenib. The U.S. National Cancer Institute (NCI) has awarded the Medical University of South Carolina (MUSC) $1.8 million to fund the phase II YELIVA study. The NCI grant is for five years.
Radiopaque Bead Treatment at Mount Sinai ‘potential game-changer’ for Hepatocellular Carcinoma
Bead treatment using M1 Lumi beads uses a catheter to deliver radiopaque beads coated in doxorubicin directly to the tumor bed. Radiopaque technology allows doctors to monitor delivery via x-ray and destroys tumors in two ways: by injecting the drug to kill the tumor and by blocking blood supply to the tumor. Another advantage of radiopaque bead treatment over conventional TACE (transarterial chemoembolization) is reduced toxicity to the patient. According to Edward Kim, MD, Director of Interventional Radiology at Mount Sinai, “My hope is that, through prospective clinical studies, we can generate meaningful data that can inform us if improved visualization and technique will translate into increased objective response and, ultimately, improved OS. Historically, OS is approximately 16 months for patients with untreated intermediate-stage liver cancer. The initial studies with conventional chemoembolization extended that survival to 20 months. Now, we are getting data with the new platforms going out as far as 45 months.”
Risk Factors for Hepatocellular Carcinoma
VIDEO A panel of researchers and doctors discuss key risk factors for HCC, including hepatitis C, hepatitis B, alcoholic cirrhosis and non-alcoholic steatohepatitis (NASH).
New Report Examines the Global Metastatic Hepatocellular Carcinoma (HCC) 2016
“The report provides comprehensive information on the therapeutics under development for Metastatic Hepatocellular Carcinoma (HCC), complete with analysis by stage of development, drug target, mechanism of action (MoA), route of administration (RoA) and molecule type. The report also covers the descriptive pharmacological action of the therapeutics, its complete research and development history and latest news and press releases.”
Mothers Receive Inadequate Systemic HBV Care Following Pregnancy
According to a retrospective study, most mothers with chronic HBV infection following their pregnancy received inadequate liver test function measurements and HCC screening. Researchers examined 243 hepatitis B surface antigen-positive mothers at Massachusetts General Hospital. They found that 37% of mothers were diagnosed the first time at their prenatal visit and that 49% of overall patients saw no specialist at all. In 34% of patients, HBV DNA was not measured in a timely manner and in 26% of patients not measured at all. “The emphasis on preventing vertical transmission to the infant from the chronically infected mother is appropriate, but should not neglect the follow-up care of the mother, particularly since maternal health is critical for optimal infant outcomes,” the researchers wrote.
New Hepatocellular Carcinoma Prognostic Model Improves Prediction of Patient Survival
A prognostic system ITA.LI.CA, built on previous HCC prognostic models, integrates tumor staging, functional status, liver function and alpha-fetoprotein level to better predict patient survival. Researchers used ITA.LI.CA. data from 5,290 Italian HCC patients to create the system, which compared favorably to other HCC prognostic systems. In a Perspective on the study, Neehar Parikh of University of Michigan, Ann Arbor, Michigan (US) and Amit Singal of UT Southwestern Medical Center, Dallas, Texas (US) (both uninvolved in the study) discuss why ITA.LI.CA is timely and provides an advance, and propose next steps. On this study's impact, they say, "[t]his system is an important iteration in the evolution of staging for HCC, and, while it enters a crowded field, the ITA.LI.CA staging system is a worthy entrant."
Dr. Geschwind on Locoregional Therapy for Patients with Liver Cancer
VIDEO “Jeff Geschwind, MD, professor and chairman, Radiology and Biomedical Imaging, Yale Cancer Center, discusses locoregional treatment options for patients with Hepatocellular Carcinoma (HCC). Regardless of whether a patient has localized or metastatic HCC, practitioners are able to deliver treatment to patients through the hepatic artery. Such therapies include chemotherapy and radiation therapy in order to maximize the potency, but minimize toxicity.”Resectability of HCC25 Apr 2016VIDEO A panel of researchers and surgeons weigh the pros and cons of transplant versus resection in patients with HCC.
Risk of Liver Cancer From Hepatitis B Persists Even After Clearing the Virus
US Centers for Disease Control researchers followed 1346 chronic HBV patients for up to 31 years: 238 who had resolved HBV infection and 435 who had not. Liver cancer risk in resolved HBV-patients vs. unresolved was similar. "Since the risk of liver cancer persists among adults with apparent cure of the infection, they might still need to be followed closely," said Dr. Prabhu Gounder, lead author of the Alimentary Pharmacology & Therapeutics article.
Successful Treatment for Hepatitis C Reduces Risk of Liver Cancer Later in Veterans
Baylor College of Medicine researchers studied data from 33,005 veterans with hepatitis C who received treatment at VA hospitals, and of whom 10,817 patients were cured. The team then tracked the veterans’ risk of HCC development and found that successful antiviral treatment for HCV was linked to a reduction in risk of cirrhosis, HCC and overall mortality, no matter the age of the patient. “Patients with cirrhosis or diabetes or those who are older than 55 who get cured of hepatitis C need continued surveillance according to current guidelines,” said Dr. Hashem El-Serag chief of gastroenterology and hepatology at Baylor. “The time of cure is essential for determining prognosis. High emphasis should be given to increasing screening and diagnosis of hepatitis C before those infected develop cirrhosis, through assessment of degree of liver fibrosis, said El-Serag.”
Multidisciplinary Care in Hepatocellular Carcinoma
A panel of researchers and physicians discuss treatment options for HCC in a video.
Dr. Hao Zhu at UT Southwestern in Dallas found that blocking the Arid1a gene in mice significantly increases the ability of the liver to heal itself from liver cancer and even generate new, healthy liver tissue. Stand Up To Cancer awarded the $750,000 grant to Zhu in keeping with its goal to award early-career scientists in their high-risk, high-reward projects in cancer research. “Dr. Zhu’s research is providing important new insights into cancer biology. His drive to translate his findings to patients and his collaborative approach to science make him a valued member of Children's Research Institute. We are proud that the grant from Stand Up To Cancer will further his important work.” said Dr. Sean Morrison, CRI Director, Professor of Pediatrics at UT Southwestern, and a Howard Hughes Medical Institute Investigator. Dr. Morrison holds the Mary McDermott Cook Chair in Pediatric Genetics.
Hepatocellular Carcinoma Incidence to Increase Through 2030
The Journal of Clinical Oncology expects the rate of HCC to increase among blacks and Hispanics through 2030. The researchers analyzed data from the Surveillance, Epidemiology and End Results (SEER) 18 Registry Database for patients aged 35-84 from 2000 – 2012 to predict incidence rates. The Journal also found that projected HCC incidence during this timeframe was 3.5 higher for men than for women. “A sensitivity analysis showed that if 50% of HCV infections are treated by 2030, HCC rates will “plateau” by 2025. If 80% are treated by 2030, then HCC rates will begin to decrease, according to the research.”
Novel Therapies on the Horizon in Hepatocellular Carcinoma
A summary of ongoing HCC trials in a first-line setting: Nivolumab (Opdivo) is a monoclonal antibody that allows the immune system to attack the tumor. Lenvantinib, currently approved in the treatment of thyroid cancer, is in a phase I/II safety and efficacy study for HCC. Second-line setting treatments: Regorafenib, previously approved for gastrointestinal stromal tumors and previously treated metastatic colorectal cancer, is being investigated for its effectiveness in disrupting HCC tumors. Cabozantinib, a small-molecule inhibitor approved for treatment of thyroid cancer, has showed promising results in treating HCC in a phase II trial and a phase III trial is ongoing. Tivantinib is in a phase II trial as a predictor of HCC tumor progression.
Deciding on the Best Treatment in Patients With Various Types of Hepatitis B
It is estimated that there are 350 million hepatitis B (HBV) carriers worldwide with complications resulting in 600,000 deaths every year. There are as many as 560,000 new cases of HBV-related HCC resulting in one-half of liver cancer deaths annually. There are approximately 850,000 Americans with chronic HBV-infection, with a 2-3 fold greater incidence among non-Hispanic blacks than among the general population. “The AASLD (American Association for the Study of Liver Diseases) recommends antiviral therapy for adults with immune-active chronic hepatitis B (HBeAg-negative or HBeAg-positive) to decrease the risk for liver-related complications.”
In Phase III of the ReLive trial, Livatag® was delivered to HCC cells via nanoparticles to short-circuit the body’s drug resistance by masking the anticancer agent. Final results supported use of Livatag® for treatment of patients with HCC. Graham Dixon, PhD, Chief Scientific Officer of Onxeo, commented, “These are important findings as they confirm that the underlying mechanism of action of Livatag®’s nanoformulation effectively accumulates doxorubicin specifically in the liver and evades tumor cell resistance mediated by multiple drug resistance MDR efflux pumps, enabling an efficacious and safe approach to cancer treatment. These results further support our ongoing Phase 3 ReLive study of Livatag® for the treatment of patients with advanced HCC, for which we anticipate preliminary data readout mid-2017.”
Hepatocellular Carcinoma Clinical Trials Review By Global Market Researcher Store
This review provides a glimpse of the global HCC trial landscape, provides top-level data on these trials and reports on the companies searching for a cure for HCC.
Massive Whole-Genome Study Finds Six Types of Liver Cancer
Japanese researchers conducted a whole-genomestudy of 300 liver cancer patients, the largest genomic study ever, and found that the cancer is caused by gene mutations and abnormalities in almost 40 genes, 10 of which had never been associated with HCC before. According to how these factors are mixed, liver cancer can be divided into roughly six types. “There are not a whole lot of molecular target therapy options for liver cancer patients,” Hidewaki Nakagawa, a Riken Institute researcher at the University of Tokyo, said by phone Tuesday. “Right now, we have only one such drug approved, called Sorafenib, but whether the drug is effective or what molecule it actually targets is not really known. The whole-genome analysis could change that, paving the way for personalized medicine.”
Cancer Thwarts Treatment By ‘Stealing’ Blood Vessels
British researchers studying mice with HCC found that the cancer became resistant to drugs over time and learned to steal blood vessels from surrounding tissue in order to survive. The researchers found that the process, called vessel co-option, was reversible when treatment was stopped and the tumors resumed new vessel growth on their own. This could explain why some patients respond to the same cancer-fighting treatment after a treatment holiday. “Our study is the first to show that cancers can adapt to treatment by actively co-opting blood vessels from nearby tissues as a mechanism of drug resistance,” said study co-leader Professor Robert Kerbel and lead author Elizabeth Kuczynski from the Sunnybrook Research Institute, University of Toronto. “In the future, we hope our results will lead to the development of new drug types that target vessel co-option. We believe that drugs which are designed to target vessel co-option could be particularly effective when used alongside existing therapies that block new blood vessel growth.”
Incidence of Hepatocellular Carcinoma May Decline
National Cancer Institute researchers studied data from the SEER 18 Registry Databases for Americans aged 35-84 from 2000-2012 and found that, while all ethnic groups showed an increased incidence of HCC, the forecast is for that incidence to likely decrease by 2030. By that year, the researchers predict that Asian/Pacific Islanders will have the lowest rate of HCC while Hispanic men will have the highest rate and Hispanic women the second highest. “Although liver cancer has long had some of the most rapidly increasing incidence rates, the decreasing rates already seen among Asian/Pacific Islanders, individuals younger than 65 years, and birth cohorts after 1959 suggest that we may see continued declines in the incidence of HCC in future years,” stated Jessica L. Petrick, PhD., MPH. of the NCI.
Data from a study of HCV patients taking direct-acting antiviral treatments (DAAs), who had previously survived HCC, showed that 29% of those patients developed the disease again. In the Italian study of 344 HIV-negative patients with HCV-related cirrhosis, all had received one of the following DAA treatment combinations: sofusbuvir and simeprevir (34%), 3D combination (22%), sofusbuvir and ribavirin (17%), sofosbuvir and daclatasvir (16%), and sofosbuvir and ledipasvir (10%). "These initial findings provide important insight to how hepatitis C management strategies could be developed to detect HCC early in patients who are most at risk," said Professor Laurent Castera, EASL Secretary General. "These findings deserve further investigation given their clinical significance."
Onxeo Announces Positive DSMB Recommendation to Continue Livatag ® ReLive Study in HCC
ReLive, a randomized Phase III international trial to evaluate the efficacy of intravenous delivery of Livatag ® in advanced HCC patients as a secondary treatment after sorafenib, has received the green light from the Data Safety Monitoring Board of Europe for the eighth time. The delivery of Livatag to HCC cells via nanoparticles short-circuits the body’s drug resistance by masking the anticancer agent. “This eighth positive recommendation from our independent board of experts once again confirms Livatag®’s safety profile, based on data collected from a growing number of patients. We remain very confident in the potential of this innovative product based on a novel nanoparticle formulation, allowing it to overcome tumor resistance to traditional chemotherapy,” stated Judith Greciet, Onxeo CEO.
Early clinical data shows that the Surefire Infusion Technology system, which uses a precision catheter to deliver drug eluting yttrium-90 microspheres to primary liver cancers that many times contain regions of high pressure and no blood flow, showed an 80% complete tumor response and a 93% objective tumor response. In the retrospective review, 11 patients with 21 separate lesions were treated with Surefire in chemoembolization procedures over 12 months. “This pilot study shows that site-specific delivery of therapy to cancers of the liver with the Surefire Infusion System can achieve very high complete response rates,” said James E. Chomas, President and CEO of Surefire Medical. “There is a growing body of evidence that achieving a complete response on a single procedure leads to significantly longer overall patient survival. Our technology allows Interventional Radiologists to achieve a new level of control and to standardize therapy delivery to the tumor.”
TARGET (Therasphere® Advanced Dosimetry Retrospective Global Study Evaluation in Hepatocellular Carcinoma Treatment) will evaluate the effectiveness of Therasphere® 90Y radioembolization on normal tissue and the tumor absorbed dose in HCC patients. Secondary endpoints of the study are incidence of serious adverse events, clinical laboratory assessment, select dose related adverse events, objective tumor response and overall survival. “The objective of the study is to provide treating physicians with clinical data that will allow a more tailored dosimetry approach for treating patients. By taking into account the absorbed dose to tumor and normal liver, physicians will have the opportunity to better personalize 90Y radioembolization therapy."
The PHOCUS trial will enroll 600 advanced liver cancer patients and give one group Pexa-Vec followed by sorafenib and the other group sorafenib alone. The primary objective is overall survival of patients, with secondary endpoints including time to tumor progression, progression-free survival, disease control rate and overall response rate. The company has enrolled its first U.S. patient in the multinational, randomized phase III trial at the University of Tennessee Medical Center in Knoxville, Tennessee.
Tissue Regeneration Generated Through Gene Suppression
In mammals, the liver is the only organ that has the capability to grow new tissue and can regenerate up to 70% of its tissue after injury. Scientists at Children’s Medical Research Center Institute (CRI) at UT Southwestern Medical Center have discovered that when an individual protein-coding gene is inactivated liver tissue regeneration in mammals is promoted. "This research gives us ideas about new ways to treat liver damage or chronic liver disease," explained senior study author Hao Zhu, M.D., assistant professor at CRI.”
Nucleos(t)ide Analogue Therapy Reduces Risk for HCC Recurrence in HBV
In a cohort study of over 2000 patients with chronic HBV and HCC, those treated with nucleos(t)ide analogue therapy had a reduced incidence of HCC returning. Over a median follow-up of 2 years, HCC recurrence/mortality was 36.7%/47% in untreated patients, respectively, while in treated patients it was 22.3%/31.1%, respectively. “Our findings show that nucleos(t)ide analogues treatment reduces the risk of HCC recurrence in patients with chronic hepatitis B treated by surgical resection,” the researchers concluded.
Phase III Study of Tivantinib in Hepatocellular Carcinoma Continues
The METIV-HCC trial is a collaboration between Arqule, Inc. and Daiichi Sankyo, Inc., that will include at least 300 patients with HCC and MET-high tumors. The patients will be given tivantinib, a selective inhibitor of the c-MET receptor, with overall survival as the primary endpoint. The independent data monitoring committee (DMC) has given approval for the study to proceed to its final analysis.
Metabolic Disorder Largest Risk Factor of Hepatocellular Carcinoma
Results of a study of US Medicare recipients with HCC diagnosed from 2000 – 2011 found that 32% of HCC cases were attributable to metabolic disorders, 20.5% to HCV infection, 13.4% to alcohol, 9% to smoking 4.3% to HBV and 1.5% to genetic disorders. The study found that HCC was more likely to be caused by metabolic disorders in Hispanics and whites, while HCV was a major cause for blacks and Asians. Metabolic disorder-related HCC increased by 10% while HCC caused by alcohol-related disorders and HCV infection remained stable.
Questions Arise Regarding Embolization in Liver Cancer
From 2007 – 2012, several researchers conducted a randomized study of 101 HCC patients to compare embolization using microspheres alone to chemoembolization using doxorubicin-eluting beads. Adverse events were similar in the trial and median overall survival was 19.6 months versus 20.8 months, respectively. Dr. Ghassan Abou-Alfa, MD, one of the study authors had this to say in a Q&A. “No doubt that this study has shown no difference between embolization using microspheres and chemoembolization, and obviously it brings into question the current practice of chemoembolization. Nonetheless, as chemoembolization has been an embedded practice around the world... it would be hard to believe that we would be able to change the concept of chemoembolization to bland embolization, just by the data present.”
Development and Novel Therapeutics in Hepatocellular Carcinoma: A Review
This review summarizes the epidemiological trend, risk factors, prevention strategies such as vaccination, staging, current novel therapeutics, including the drugs under clinical trials, and future therapeutic trends for Hepatocellular Carcinoma (HCC).
Roche Boosts Cancer Portfolio with $1Bn Blueprint Deal
The company’s immunotherapy, BLU-554, is in preclinical development and is expected to start clinical testing in Hepatocellular Carcinoma later in 2016.
INTUVAX is a treatment for solid tumors that injects activated white blood cells from healthy donors into liver tumors to generate an inflammatory response, which activates the body’s own immune system to fight HCC. Of nine patients that received full treatment with INTUVAX in a second-line setting, five have passed the expected median survival date and four are still alive. One patient in the extended phase I/II liver cancer trial has received INTUVAX as a first-line treatment. "We look forward to the opportunity to give INTUVAX as first-line treatment in combination with particularly Sorafenib since Sorafenib is known to be able to dampen immunosuppression by reducing the number of myeloid suppressor cells in the bone marrow, blood and liver tumors in mouse models. Just as INTUVAX appears to work synergistically with Sunitinib in our Phase I/II study in renal cancer, and with gemcitabin and cisplatin in the treated patient with bile duct cancer, we believe that INTUVAX in combination with Sorafenib can generate a synergistic anti-tumor effect in patients with liver cancer", says Immunicum's Chief Scientific Officer, Alex Karlsson-Parra.
This Phase II Liver Cancer Data Could Boost Arbutus Going Forward
Arbutus, formerly Tekmira, expects to report topline data from its phase II trial of TKM-PLK1 in the first half of 2016. TKM-PLK1 selectively suppresses the replication of cancerous liver cells, while at the same time causing them to self-destruct in anticipation of absorption by the body’s immune system.
Cancer Deaths Drop, With Liver Cancer the Exception
The CDC’s annual Report to the Nation on the Status of Cancer says that more people are dying from liver cancer due to higher rates of diabetes, obesity, alcohol abuse and the ravages of hepatitis C. Between 2008 and 2012, the rate of liver cancer rose an average of 2.3% each year and the death rate from liver cancer rose an average of 2.8% and 3.4% for men and women each year, respectively. From 2003-2012 the overall cancer death rate fell by 1.5%.
Illinois University researchers studied four groups of mice: Some were on a Western diet high in sugar and fat and some were in a control group; some were given broccoli and some were not. Mice on the Western diet had more tumors with nodules of a greater size than the other groups, but when broccoli was added to the diet the number of nodules decreased. “We found that the Westernized diet did increase fatty liver, but we saw that the broccoli protected against it,” stated Professor Elizabeth Jeffery, from Illinois University. “Broccoli stopped too much uptake of fat into the liver by decreasing the uptake and increasing the output of lipid from the liver.”
Celsion (CLSN) Launches OPTIMA Study in China
Thermodox® is the company’s heat-activated liposomal encapsulation of doxorubicin, which is combined with optimized radio frequency ablation (RFA) to treat primary liver cancer. Phase III of OPTIMA expects to enroll 550 patients and has thus far enrolled patients at 50 clinical sites in North America, Europe and the Asia Pacific. Celsion plans to open up to 20 more sites in China with an enrollment of 200 patients. “The design of the OPTIMA Study is supported by a retrospective analysis of a large subgroup of 285 patients in the Company's previous 701 patient HEAT Study in primary liver cancer. In a subgroup of 285 HEAT Study participants, ThermoDox® plus standardized RFA demonstrated a statistically significant improvement in survival of over two years compared to standardized RFA alone. In this large subgroup, the median overall survival in the ThermoDox® plus standardized RFA arm was approximately 80 months (6 ½ years), which is considered a curative treatment for HCC.”
Major Liver Cancer Study Completes Palliative Cohort Enrollment
SORAMIC (Sorafenib and Micro-therapy Guided by Primovist ®-Enhanced MRI in Patients with Inoperable Liver Cancer) is the first randomized controlled trial combining sorafenib and liver-directed selective internal radiation therapy (SIRT) with Y-90 microspheres (SIR-Spheres®). “Patients with primary liver cancer who took part in the palliative cohort of the SORAMIC study were not eligible for resection or ablation, and were not suitable candidates for trans-arterial chemoembolization (TACE), an interventional technique for treating liver tumors locally, with chemotherapy-eluting beads. Results of the SORAMIC study are expected in 2018.”
Antioxidants Promote the Growth of Liver Cancer Cells
University of Hong Kong researchers have found that in mouse models for liver cancer excessive reactive oxygen species (ROS), or free radicals, caused more oxidative stress, which hindered cancer cell growth. The study found that oxidative stress decreased as more antioxidants are produced which leads to growth in cancer cells. The researchers said, “Liver cancer patients are advised to have a balanced diet and they should note that a high intake of antioxidant supplements may not be beneficial to health.”
Probiotics Shown to Suppress Liver Cancer in Mice
Hong Kong researchers have created a probiotic cocktail, called Prohep, which they used in a first-of-its-kind study to show the benefits of probiotics on HCC. “In our study, the impact of the anti-inflammatory molecules produced by the beneficial bacteria was not directly on the inflammation site. These molecules reduced the frequency of a particular type of immune cells in the gut, Th17 cells, that promote inflammation,” said Associate Professor Gianni Panagiotou from Hong Kong University. “Since inflammation is a key process in cancer progression, by reducing Th17 frequency in the gut, and subsequently their recruitment through blood circulation in the liver, we succeeded in interrupting tumor growth.”
Dendritic Cell Vaccine Inhibits Tumor Progression in Preclinical Liver Cancer Model
Saronic Biotechnology’s SBI1997 is an autologous dendritic cell immunotherapy for HCC that assists each patient’s immune system to identify tumor-specific antigens and destroy cancerous cells after surgery. Preclinical vaccine results showed a survival rate of 90% for DC-vaccine treated mice versus a 5% survival rate for untreated mice after 60 days. Saronic has started clinical testing of SBI1997 on HCC patients and plans to launch a randomized, phase I/II clinical trial in 2016.
German Biotech Wins FDA Approval for New Liver Cancer Trial
Resminostat is Munich-based 4SC’s investigational new drug (IND) for HCC that reprograms the behavior of cancer cells. The company will conduct trials in the US to determine the efficacy of Resminostat alone and in combination with sorafenib (Nexavar).
Multiple studies were analyzed for long-term outcomes for survival from radiofrequency ablation versus resection. In six studies, rates of 3-year OS (overall survival), 5-year OS, 3-year DFS (disease-free survival) and 5-year DFS were much lower in the radiofrequency ablation group versus the resection group. In a different group of 10 studies, 3-year OS, 5-year OS, 3-year DFS and 5-year DFS were significantly lower for the radiofrequency ablation group compared to resection, as well. Conclusion, long-term survival is higher with resection compared to radiofrequency ablation.
MEP1A Gene Expression Predicts HCC
The molecular diversity of HCC makes it difficult to predict a patient’s prognosis in clinical practice, but researchers have found that the MEP1A gene is a unique predictor of HCC and the development and rate of progression of the disease. The analysis, published in Hepatology, shows that evidence of MEP1A in HCC tumor cells was a verifiable and legitimate risk factor that affected survival following resection. “Our results suggest that MEP1A is a novel prognostic predictor in HCC and plays an important role in the development and progression of HCC,” concluded the researchers.
Cirrhosis, HCC Risk in HCV Reduced Significantly With These Statins
Findings from a study published in the online journal Hepatology found that the statins atorvastatin and fluvastatin were linked to a reduction in the occurrence of cirrhosis and HCC in chronic HCV patients.
Effimune, In Cell Art Launch Cancer Immunotherapy Collaboration
Effimune’s unique cancer immunotherapy strategy will use In Cell Art’s Nanotaxi ® technology to produce antibodies involved in controlling the immune reaction of liver cancer tumor cells. “Effimune and In Cell Art reason that enabling patients to produce their own therapeutic antibodies offers two advantages over conventional methods: a significantly reduced risk of intolerance and reduced costs from achieving economies of scale in terms of processes, numbers of injections, and production expense.”
FDA Grants Breakthrough Therapy Designation To Durvalumab For Bladder Cancer
Durvalumab is in trial as a monotherapy and in combination with tremelimumab (AstraZeneca and Medimmune) in several other cancers, including Hepatocellular Carcinoma.
Adding Everolimus to Sorafenib Not Effective for Hepatocellular Carcinoma
In an international phase 2 trial of 106 patients with unresectable metastatic HCC, everolimus combined with sorafenib did not improve outcomes compared to sorafenib alone and was actually more toxic to patients. The sorafenib monotherapy 12-month progression-free survival rate was 70% versus 68% with sorafenib and everolimus in combination; progression-free survival was 6.6 months and 5.7 months, overall survival was 10 months and 12 months, respectively.
In a Phase II study of 44 patients with advanced HCC where surgery was not an option and sorafenib had failed, patients received bevacizumab and erlotinib in combination at two-week intervals. The 16-week progression-free survival rate was 43%, median overall survival duration was 9.9 months and median time to progression was 3.9 months. Conclusion: “Bevacizumab plus erlotinib was tolerable and showed a signal of survival benefit in the second-line setting for patients with advanced HCC. Because standard-of-care options are lacking in this setting, further studies to identify predictors of response to this regimen are warranted.”
BTG, Philips Roll Out First Cancer Embolic Bead Visible Via Real-Time Imaging
The company’s LC Bead Lumi is a preformed, deformable, opaque microsphere that allows surgeons to monitor, in real-time, whether the beads remain in the intended location during embolization. “The aim with this new radiopaque embolic bead and visualization technology is to provide clinicians like me the ability to make real-time adjustments while conducting the embolization procedure, so that we can optimize the patients’ treatment and hopefully improve targeting accuracy,” stated Dr. Bradford Wood, director of the NIH Center for Interventional Oncology and Chief of Interventional Radiology.
Experimental Nanoparticle Therapy Shows Promise for Fighting Primary Liver Cancer
Researchers at UT Southwestern Medical Center have shown that low-density lipoproteins (LDL) and fish oil, delivered as a nanoparticle therapy, is effective in killing HCC cells while leaving surrounding healthy cells unharmed. Several studies have shown that fish oil, rich in omega-3 fatty acids, has been associated with cancer prevention, but this is the first study to show the effectiveness of omega-3s against established tumors. “This research study clearly demonstrates the anticancer potential of omega-3 fatty acids,” stated Dr. Ian Corbin, Assistant Professor in the Advanced Imaging Research Center (AIRC) at UT Southwestern. He added, “... that while the study showed significant cancer cell toxicity, it is too soon to tell whether the approach is able to kill every cancer cell.”
Hepatocellular Carcinoma Market Report—Pipeline Review H2 2015—Research and Markets
“This report provides comprehensive information on the therapeutic development for Hepatocellular Carcinoma, complete with comparative analysis at various stages, therapeutics assessment by drug target, mechanism of action (MoA), route of administration (RoA) and molecule type, along with latest updates, and featured news and press releases. It also reviews key players involved in the therapeutic development for Hepatocellular Carcinoma and special features on late-stage and discontinued projects.”
Study Challenges Use of Doxorubicin Beads for Hepatocellular Carcinoma
Researchers at Memorial Sloan Kettering Cancer Center in New York conducted a double-blind study involving 101 HCC patients randomly assigned to undergo embolization with doxorubicin-loaded microspheres versus microspheres alone. The doxorubicin group had a 6.0% response rate versus 5.9% for the microspheres alone group; overall survival was 20.8 months versus 19.6 months, respectively. “There was no apparent difference between the treatment arms,” the authors concluded. “These results challenge the use of doxorubicin-eluting beads for chemoembolization of HCC.”
Regional Liver Cancer Registry To Be Set Up
The National Cancer Center Singapore (NCCS) has entered a partnership to start a registry to collect liver cancer data in 7 – 8 countries. Data, such as when a patient is diagnosed, if cost is an issue in choosing the type of treatment and whether early screening can save lives will be collected to try and understand cancer disease patterns and the relation to an individual’s genetic information. “Having this kind of information allows policy agencies to allocate their resources accordingly in a way that benefits the patients most,” stated Professor Pierce Chow, senior consultant surgeon at NCCS.
Latest Reports: Metastatic Liver Cancer Market 2014 to 2022 by Acute Market Reports
An overview of the Metastatic Liver Cancer pipeline that discusses investigational drugs from around the world covering 20 therapy areas and close to 3000 indications. The report features information on therapeutic development for Metastatic Liver Cancer “...with comparative analysis at various stages, therapeutics assessment by drug target, mechanism of action (MoA), route of administration (RoA), and molecule type, along with latest updates, and featured news and press releases.”
OPDIVO, the first PD-1 immune checkpoint inhibitor cancer treatment, provides anti-tumor activity across malignant tumors. In 2016, ONO will undertake a series of trials in Japan to assess the safety and efficacy of Opdivo against a number of indications, including Hepatocellular Carcinoma.
CARsgen Therapeutics Completes $30 Million Series B Financing
“CARSgen is harnessing CAR-T cells to target the GPC3 receptor for the treatment of late-stage Hepatocellular Carcinoma...” The company is enrolling patients in China for a phase I clinical study with results expected by the end of 2016.
Neoadjuvant Sorafenib Shows Significant Activity in HCC
Results from the phase II BIOSPHERE study showed that 24% of patients with resectable Hepatocellular Carcinoma demonstrated major tumor necrosis when treated with Nexavar preoperatively. Examination of tumor specimens found 68% of patients had some necrosis because of Nexavar treatment and the researchers found no evidence of patient resistance to the drug in this population. “Even with a short period of exposure to sorafenib, we have a good number of patients with response,” stated lead investigator Mohamed Bouattour, MD. “Even though sorafenib is not used preoperatively in clinical practice, we now know more about its mechanism of action, which we think applies to advanced HCC, as well as earlier HCC.”
Adding Doxorubicin to Sorafenib Not Effective for Hepatocellular Carcinoma
In a study of 346 advanced HCC patients with no history of prior systemic therapy, researchers discovered that doxorubicin in combination with sorafenib was less effective than sorafenib alone. For the combined therapy, median overall survival was 9.3 months versus 10.5 months with sorafenib alone. Median progression-free survival was 3.6 months and 3.2 months respectively; there were 18 deaths with combined therapy and 20 with sorafenib alone. “A total of 37.8% of patients receiving doxorubicin plus sorafenib experienced grade 3 or 4 hematologic adverse events compared with 8.1% of those receiving sorafenib; however, the rate of non-hematologic adverse events were similar between the 2 arms (63.6% and 61.5%, respectively).”
GI ASCO: AHN Research Finds SBRT Effective Option for Liver Cancer Patients
Stereotactic body radiotherapy (SBRT) uses advanced diagnostic images to map and accurately target tumors in high doses over a shorter interval than standard radiation therapy. According to data from the Allegheny Health Network, SBRT was safe and successful at controlling the growth of 96% of primary tumors and 94% of metastases over a two-year period. SBRT is effective as a bridge to liver transplant, a stand-alone treatment for inoperable liver tumors and in combination with tumor removal. “Surgery remains the gold standard for treating liver cancer, but unfortunately more than 80% of patients with liver cancer are not eligible for surgery,” stated Dr. Alexander Kirichenko, MD., Allegheny Health Network radiation oncologist. “SBRT offers these patients a safe option.”
Viread (Tenofovir, TDF) Linked With Liver Disease and Cancer
Viread (tenofovir disoproxil fumarate, or TDF), is an antiviral drug that stops human immunodeficiency virus (HIV) or HBV cells from multiplying in the body. In a cohort collaboration study begun in 1999 that followed 50,000 HIV-positive people in Australia, the U.S. and Europe, researchers discovered that for each 5 years of Viread, Zerit, Videx or Lexiva use, the rates of End Stage Liver Disease (ESLD) and HCC increased. Due to the increased risk of liver cancer or disease linked with the four drugs, the researchers suggested that “intensified monitoring of liver function should hence be considered among all individuals exposed [to these drugs] for longer time periods.” “They further concluded that the association of Viread with ESLD and HCC, unrelated to viral hepatitis, called for further study.”
Can-Fite BioPharma (CANF) Updates on Expected Clinical Milestones for 2016
CF102 is a small, orally bioavailable drug that has shown strong anti-tumor effects and has induced death of liver cancer cells. In the first half of 2016, the company expects to complete enrollment of 78 patients in the phase II trial for CF-102 to treat Hepatocellular Carcinoma in the U.S, Europe and Israel. The drug has received Fast Track Designation by the U.S. FDA as an HCC second-line treatment and the Israeli Ministry of Health has approved CF-102 for Compassionate Use for liver cancer patients.
David Bowie Died of Liver Cancer, Friend and Collaborator Says
The rock icon had been battling cancer for 18 months, but no details were released. Ivo Van Hove, a Belgian theater director who collaborated with Bowie on a production of “Lazarus,” told a Dutch radio station that the icon had liver cancer. “I saw a man fighting. He fought like a lion and kept working through it all. I had incredible respect for that,” Van Hove said.
Scientists Root Out the ‘Bad Seeds’ of Liver Cancer
The stem cell marker NANOG controls the expression of genes that become energy sources for stem cells that later develop into tumors. NANOG is barely present in early-stage cancer, but is plentiful in stage III liver cancer and helps the HCC fight treatment and cause relapse. “If we shut down this alternative pathway, the liver cancer will become sensitized to chemotherapy again,” said Keigo Machida, senior author and associate professor of molecular microbiology and immunology at the Keck School of Medicine, USC. “In the future, we might be able to give liver cancer patients a shot that will infuse NANOG-targeted therapy into the blood stream. Wherever blood circulates, we will be able to deliver new instructions to the bad seeds of cancer.”
Pexa-Vec is viral therapy designed to target and destroy cancer cells through the breakdown of cancer cell replication, the reduction of blood flow to the tumors and by stimulating the body’s immune system to fight the cancer cells. The PHOCUS trial will enroll 600 patients who have received no prior systemic treatment for their cancer. Participants in the randomized trial will receive Pexa-Vec followed by sorafenib or sorafenib alone. “We are still desperately in need of additional treatment options for advanced liver cancer. Cancer immunotherapy holds much promise, and I’m greatly looking forward to having the opportunity to evaluate Pexa-Vec in patients with advanced liver cancer,” stated Ghassan Abou-Alfa, M.D., medical oncologist at Memorial Sloan Kettering Cancer Center.
Taiwan Researchers Link Air Pollution to Liver Cancer
A Taiwanese scientific team followed 23,820 people aged 30 and above from 1991-2015 and tracked their exposure to air pollution and their incidence of HCC. The team discovered that patients exposed to fine particulate matter at 2.5 parts-per-million (PM 2.5) had a rise in the amount alanine aminotransferase in their body, a type of enzyme used to measure liver health. “While it is widely knows that PM 2.5 contributes to heart and lung diseases, our findings provide more evidence to the health hazards of such pollutants,” said Yan Hwai-I, the paper’s author and an associate research fellow at AS Genomics Research Center.
How ‘Golden Spice’ Saffron Helps Keep Liver Cancer at Bay
A new study conducted at the United Arab Emirates University found that saffron’s main biomolecule, crocin, displayed chemopreventive action against chemically induced liver cancer in rats. The team focused on the anti-oxidant and anti-inflammatory mechanisms of crocin in vivo and in vitro to learn about its anti-tumor effects. “Taken together, our findings introduce crocin as a candidate chemopreventive agent against HCC,” the authors concluded.