Diabetes Thought to Increase Risk for Hepatic Cancer

A retroactive study presented at the 2015 Annual Meeting for the American College of Gastroenterology (ACG) suggests that diabetes increases the risk for hepatocellular carcinoma. Hepatocellular carcinoma is the most common form of liver cancer. The disease generally occurs secondary to hepatitis C infection or in cirrhosis from other causes.

The study authors used data from MarketScan, which is a database for insurance claims of all kinds. They found 7,473 patients with hepatocellular carcinoma. The authors also included 22,110 controls matched for comorbidities, age, sex, and gender, leading to a 1-to-3 ratio of subjects to controls for 99% of the case subjects. The patients included in the case group had hepatocellular carcinoma with hepatitis C with DM, without DM, and DM alone. The study also looked at the impact of metabolic syndrome, hypertension, and dyslipidemia.

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Phase I/II Opdivo (nivolumab) Trial Shows Bristol-Myers Squibb’s PD-1 Immune Checkpoint Inhibitor is First to Demonstrate Anti-Tumor Activity In Patients With Hepatocellular Carcinoma

• Interim results show favorable safety profile of Opdivo, and durable responses in previously-treated patients
• Overall survival rate of 62% at 12 months observed at this interim analysis
• Hepatocellular carcinoma is the second most frequent cause of cancer-related death worldwide and remains an area of significant unmet medical need
• Patients with hepatocellular carcinoma who have relapsed or have disease progression, following standard of care, have a median survival with best supportive care of ~7 to 8 months

PRINCETON, N.J.--(BUSINESS WIRE)--Bristol-Myers Squibb Company (NYSE:BMY) today announced results from an interim analysis of CA209-040, a Phase I/II dose-ranging trial evaluating the safety and anti-tumor activity of Opdivo (nivolumab) in previously-treated patients with hepatocellular carcinoma (HCC) or advanced liver cancer. Initial findings demonstrated that the estimated survival rate in evaluable patients (n=47) was 62% at 12 months. Results also show the safety profile of Opdivo is generally consistent with that previously-reported for Opdivo in other tumor types. These data will be featured today, May 29, during the 51st Annual Meeting of the American Society of Clinical Oncology (ASCO) press briefing at 1:00 – 2:00 p.m. CDT and presented on Saturday, May 30 from 8:27 a.m. – 8:39 a.m. CDT (Late Breaking Abstract #101).

“Hepatocellular carcinoma is an aggressive and fatal cancer, comprising 90 percent of all liver cancer in adults worldwide with limited therapeutic options for patients with advanced stage disease; no treatment advances have been made for patients who fail to respond or progress on the current standard of care,” said Anthony B. El-Khoueiry, MD, lead study author and associate professor of clinical medicine and phase I program director at the University of Southern California Norris Comprehensive Cancer Center. “These preliminary data are encouraging and support the ongoing evaluation of nivolumab in this patient population, as they show promising preliminary survival data, and durable partial or complete response in one out of five nivolumab-treated patients, with many others experiencing stable disease.”

More than 700,000 people around the world are diagnosed with HCC each year with a majority of all HCC cases caused by infection with the hepatitis B virus (HBV) or hepatitis C virus (HCV), making HBV/HCV the most common risk factor for liver cancer worldwide. Patients with advanced HCC receiving the current standard of care have a median overall survival of less than 1 year. For patients who have relapsed or have disease progression, median survival with best supportive care is approximately 7 to 8 months.

“Bristol-Myers Squibb’s experience in hepatitis and Immuno-Oncology make us poised as leaders to advance Opdivo into additional studies of hepatocellular carcinoma,” said Michael Giordano, senior vice president, Head of Development, Oncology, Bristol-Myers Squibb. “Opdivo has demonstrated improvements in survival in a number of different tumor types. We are excited that this trial has shown the potential that this may extend to advanced liver cancer and hope to confirm these findings in future trials.”

About the CA209-040
CA209-040 is a Phase I/II dose-ranging trial that evaluated the safety and anti-tumor activity of Opdivo in patients with HCC, the majority of whom had received prior treatment. The trial included 47 HCC patients who were enrolled into one of three treatment arms depending on whether or not they were infected with HCV or HBV. Patients enrolled in the trial received Opdivo doses ranging from 0.1 – 10 mg/kg intravenously every 2 weeks for up to 2 years. The primary objective was safety, tolerability, dose limiting toxicities, and maximum tolerated dose. Anti-tumor activity was a secondary objective (using RECIST 1.1 criteria), and overall survival was an exploratory objective.

As of this interim analysis, 62% of patients in the study were still alive after 12 months. Eight (19%) patients (of 42 evaluable patients) achieved a complete or partial response, meaning that the size of their tumors measured at baseline decreased by 30–100% with Opdivo treatment. In patients with response, duration of response ranged from more than 1.4 – 12.5 months. Seventeen patients remained on study treatment and 30 discontinued treatment due to progressive disease (n=26), complete response (n=2), or adverse events (n=2).

CA209-040 is the first trial to characterize the safety profile of Opdivo monotherapy in patients with HCC, including those with HCV and HBV infections. In the trial, safety and tolerability were well-characterized, with the frequency and intensity of treatment-related adverse events (AEs) being consistent across Opdivo dose levels. The majority of side effects were mild to moderate in nature with abnormal liver enzymes (19% AST and 15% ALT), rash (17%) and elevation of amylase (15%) and lipase (17%) being the most common; the abnormal liver enzymes and elevated amylase and lipase were not accompanied by any significant clinical symptoms. Grade 3–4 treatment-related AEs were infrequent (19%). There were no treatment-related deaths reported.

About Opdivo
Bristol-Myers Squibb has a broad, global development program to study Opdivo in multiple tumor types consisting of more than 50 trials – as monotherapy or in combination with other therapies – in which more than 8,000 patients have been enrolled worldwide.

Opdivo became the first PD-1 immune checkpoint inhibitor to receive regulatory approval anywhere in the world on July 4, 2014 when Ono Pharmaceutical Co. announced that it received manufacturing and marketing approval in Japan for the treatment of patients with unresectable melanoma. In the U.S., the U.S. Food and Drug Administration (FDA) granted its first approval for Opdivo for the treatment of patients with unresectable or metastatic melanoma and disease progression following Yervoy (ipilimumab) and, if BRAF V600 mutation positive, a BRAF inhibitor. On March 4, 2015, Opdivo received its second FDA approval for the treatment of patients with metastatic squamous non-small cell lung cancer (NSCLC) with progression on or after platinum-based chemotherapy.

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Variations in Liver Cancer Attributable to Hepatitis Virus Variations

Discovery that hepatitis B and C viruses generate markedly different clinical pathologies highlights potential change in treatment plans for newly diagnosed patients

Newswise — CHICAGO —Significant clinical variations exist among patients with the most common type of liver cancer called hepatocellular carcinoma (HCC), depending on the viral cause of the disease –hepatitis B virus (HBV) or hepatitis C virus (HCV). These differences suggest that hepatitis status should be considered when developing treatment plans for newly diagnosed patients, according to researchers at The University of Texas MD Anderson Cancer Center.

These findings, from the largest single-center studies of its kind will be presented on Sunday, May 31 in an oral presentation at the 2015 Annual Meeting of the American Society of Clinical Oncology (ASCO). The research builds on previous studies of differential effects of demographics, geographical distribution and risk factors, including hepatitis status, on treatment outcomes among patients with inoperable HCC. In these earlier studies, researchers observed different outcomes based on demographics and geographic patients distribution (Asia versus Europe and USA) among patients receiving the same local or systemic therapy approaches. They hypothesized that these differences might be attributed to variations with regard to hepatitis type, among other factors.

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Evolution of Treatment for HCC: Sorafenib and Beyond

The small molecule multikinase inhibitor sorafenib remains the only molecularly targeted therapy approved by the FDA for the treatment of hepatocellular carcinoma (HCC). Ongoing clinical trials are diligently testing the potential for novel targeted agents or combination therapies to further improve patient outcomes in this setting.

Sorafenib tosylate (Nexavar) was approved by the FDA in late 2007 for the treatment of unresectable HCC, a decision based on the findings of the Sorafenib HCC Assessment Randomized Protocol (SHARP) trial.¹According to this multicenter, double-blind, phase III study, a randomized protocol of either sorafenib or placebo in 602 advanced, untreated patients with HCC, sorafenib led to statistically significant improvement in overall survival compared with placebo.

- See more at: http://www.targetedonc.com/publications/hcc-monitor/2015/may-2015/Evolution-of-Treatment-for-HCC-Sorafenib-and-Beyond#sthash.OlPiai0z.dpuf