Patients with non-operable advanced liver cancer, hepatocarcinoma, do not have many effective treatment options. This is the first report of a treatment of advanced hepatocellular carcinoma with drug Nivolumab, previously approved for melanoma treatment.
Hepatocellular carcinomas, accounting for 90% of the liver cancer cases worldwide, are significant target for drug development. Sorafenib, co-developed and co-marketed by Bayer and Onyx Pharmaceuticals as Nexavar, is the only treatment option available. In previously untreated patients with advanced disease, treatment with sorafenib shows survival extension of 3 months compared with placebo. Sorafenib is tyrosine kinase inhibitor, which targets actively dividing cells and like other chemotherapy drugs is associated with high adverse events profile. A recent study published in the Lancet Journal evaluated the efficacy and safety of Nivolumab, a new treatment option.
Chronic inflammatory conditions such as cirrhosis and viral hepatitis attract an immune response, which if properly targeted, can benefit patients and help clear cancer cells. Nivolumab, a medication approved for treatment of several types of cancers such as metastatic melanoma, renal and non-small cell lung cancer, targets immune cells attracted to the site of inflammation. Without nivolumab treatment, lymphocytes (immune cells) attracted to the inflammation, will go through programmed cell death through activation of Programmed cell death protein-1 (PD-1). Nivolumab, a fully humanized monoclonal antibody, targets and inhibits PD-1, which allows lymphocytes to work on tumor cells and fight the spread of cancer.
This is the first report on nivolumab for treatment of advanced hepatocellular carcinoma, including patients with HCV or HBV infection.
A total of 262 eligible patients were treated during 2012-2016 in open label phase 1/2 clinical study. 202 (77%) completed the treatment and are currently in follow-up phase. Patients with histologically confirmed, non-operable hepatocellular carcinoma over 18 years of age were eligible for study. The drug was administered intravenously every two weeks and tumor assessment and safety profiles were done continuously throughout the study.
This report includes the results of phase I/II of the study. The main goal of early phases is the assessment of drug safety with the goal to progress to phase III of the study to examine drug safety and efficacy in an extended patient population. Overall the safety profile of the patients treated with nivolumab was manageable, with only few new safety issues observed in addition to those described in the product monograph approved for other cancers. A substantial tumor reduction was observed in 15-20% of the patients- an improvement compared to best reported of 7% with previous treatments. Disease control was achieved in about half of the cases. The results demonstrate an encouraging response and potential for nivolumab in the treatment of hepatocellular carcinoma. A limitation of this study is the lack of randomization in treatment groups. Randomised phase III study comparing nivolumab for treatment of advanced hepatocellular carcinoma with sorafenib is underway.
Written By: Bella Groisman, PhD