Advanced, unresectable hepatocellular carcinoma (HCC) is an aggressive, difficult-to-treat disease with poor prognosis and short survival time. Until recently, sorafenib was the only approved treatment option for this malignancy. However, treatment options expanded in 2017 with the approval of the multikinase inhibitor regorafenib and the first immunotherapy, the PD-1 inhibitor nivolumab, for patients progressing on sorafenib. Nivolumab was granted accelerated approval on the basis of results from the phase I/II CheckMate-040 trial, in which nivolumab was associated with an acceptable toxicity profile and an objective response rate (ORR) of 15% in the dose expansion phase.
At the 2018 Gastrointestinal Cancers Symposium of the American Society of Clinical Oncology (ASCO), held from 18 to 20 January in San Francisco, California, United States, another PD-1 inhibitor, pembrolizumab, was shown to have efficacy in unresectable HCC.
Andrew Zhu, MD, PhD (Dana-Farber Cancer Center, Boston, Massachusetts, United States), presented results from the phase II Keynote-244 trial, which evaluated the safety and efficacy of pembrolizumab (200 mg every 3 weeks for 2 years) in 104 patients with advanced, unresectable HCC who had progressed on prior sorafenib. Pembrolizumab treatment was associated with an ORR of 16.3%, including 1 complete response and a disease control rate of 61.5%. Responses were durable with a median duration of response of 8.2 months. The median progression-free survival (PFS) was 4.8 months with an estimated 6-month PFS rate of 43.1%. At data cut-off, the median overall survival (OS) had not yet been reached. The estimated 6-month OS rate was 77.9%.
Adverse events (AEs) were consistent with the known toxicity profile of pembrolizumab. The most common treatment-related AEs of any grade were pruritus (21.2%), fatigue (12.5%), increased aspartate aminotransferase (9.6%), and diarrhea (9.6%). AEs leading to treatment discontinuation occurred in 6.7% of patients, and there was one treatment-related death from ulcerative esophagitis. Importantly, patients with hepatitis B or hepatitis C infections did not experience viral flares, and these patients responded to treatment.
Dr Zhu concluded that pembrolizumab demonstrated safety and promising efficacy in this phase II trial and that results from the ongoing phase III Keynote-240 trial, comparing pembrolizumab to placebo in previously treated patients with unresectable HCC, are expected in the near future.
For more details on this trial and other important studies across different gastrointestinal tumor types presented at the 2018 symposium in San Francisco, please view the prIME Oncology Virtual Poster Session.