The FDA has approved nivolumab injection for IV use for the treatment of patients with hepatocellular carcinoma (HCC) who have been previously treated with sorafenib. Approval for this indication has been granted under accelerated approval based on tumor response rate and durability of response. Continued approval for this indication may be contingent upon verification and description of clinical benefit in the confirmatory trials.
"Unfortunately, the majority of HCC patients are diagnosed with advanced-stage disease and are not candidates for potentially curative surgical interventions," said Adrian M. Di Bisceglie, MD, Co-Director of the Saint Louis University Liver Center and Chief of Hepatology in Missouri. "More options are needed for advanced-stage HCC patients who have failed prior systemic therapy."
HCC is often diagnosed in the advanced stage where treatment options are limited, and there is a high unmet need for patients who are intolerant to or who have progressed on sorafenib therapy.
"In recent years, there has been growing interest in leveraging immuno-oncology knowledge and discoveries to add to the treatment options available for patients with advanced-stage liver cancer," said Anthony B. El-Khoueiry, MD, lead investigator and Associate Professor of Clinical Medicine and Phase I Program Director at the Keck School of Medicine of University of Southern California (USC) and the USC Norris Comprehensive Cancer Center, Los Angeles. "The approval of nivolumab provides us with an encouraging approach and a new treatment option for appropriate patients with HCC following prior systemic therapy."
CheckMate 040 included a phase I/II, open-label, multicenter study evaluating nivolumab in patients with HCC who progressed on or were intolerant to sorafenib. In this study, 154 patients received nivolumab 3 mg/kg administered intravenously every 2 weeks. The recommended dose is 240 mg administered as an IV infusion over 60 minutes every 2 weeks until disease progression or unacceptable toxicity. Efficacy outcome measures included confirmed overall response rate (as assessed by blinded independent central review using RECIST v1.1 and modified RECIST for HCC) and duration of response.
The median age of patients participating in the study was 63 (range: 19-81), all patients had received prior sorafenib therapy and 19 percent of patients had received two or more prior systemic therapies. Patients were enrolled regardless of PD-L1 expression level and whether or not they were infected with active hepatitis B virus or active hepatitis C virus. Data from CheckMate 040 were presented at the ASCO 2017 Annual Meeting in June.
In the CheckMate 040 trial, 14.3 percent (95% CI: 9.2-20.8; 22/154) of patients responded to treatment with nivolumab. The percentage of patients with a complete response was 1.9 percent (3/154) and the percentage of patients with a partial response was 12.3 percent (19/154). Among responders (n=22), responses ranged from 3.2 months to 38.2+ months; 91 percent of those patients had responses of 6 months or longer and 55 percent had responses of 12 months or longer. The median time to response was 2.8 months (range: 1.2-7.0). The overall response rate based on modified RECIST was 18.2 percent (95% CI: 12.4-25.2; 28/154). Complete response rate was 3.2 percent (5/154); partial response rate was 14.9 percent (23/154). Responses were observed across PD-L1 expression levels.