Pembrolizumab prolonged OS compared with placebo for certain patients with advanced hepatocellular carcinoma, according to topline data released by the agent’s manufacturer.

Pembrolizumab (Keytruda, Merck) also extended PFS and induced a higher objective response rate than placebo among Asian patients with advanced HCC previously treated with sorafenib (Nexavar, Bayer) or oxaliplatin chemotherapy, results of the randomized phase 3 KEYNOTE-394 trial showed.

Pembrolizumab, an anti-PD-1 antibody, is approved in the United States for treatment of several cancer types.

The FDA granted accelerated approval to the agent in 2018 for treatment of patients with HCC who previously received sorafenib based on objective response rate and response durability data from the KEYNOTE-224 trial.

However, the subsequent KEYNOTE-240 trial failed to meet its dual primary endpoints of PFS and OS.

The FDA’s Oncologic Drugs Advisory Committee voted 8-0 in April in favor of maintaining pembrolizumab’s accelerated approval for this indication. Discussion during the committee meeting addressed how the randomized phase 3 KEYNOTE-394 could be a potential confirmatory trial to verify pembrolizumab’s benefit for this population.

KEYNOTE-394 study included 453 Asian patients with advanced HCC previously treated with sorafenib (Nexavar, Bayer) or oxaliplatin chemotherapy.

Researchers assigned patients to best supportive care plus either pembrolizumab or placebo. Patients assigned pembrolizumab received the agent via IV every 3 weeks for up to 35 cycles.

OS served as the primary endpoint. Secondary endpoints included PFS, objective response rate, duration of response and disease control rate.

The study met its primary endpoint, with researchers reporting a statistically significant OS improvement in the pembrolizumab group. The study also met its key secondary endpoints, with results showing significant longer PFS and a significantly higher ORR among patients treated with pembrolizumab.

Researchers observed no new safety signals with pembrolizumab.

Complete results from KEYNOTE-394 will be submitted for presentation at a medical meeting.

“Frequently diagnosed at an advanced stage, [HCC] has one of the highest mortality rates of solid cancers. Despite recent progress, there remains an unmet need for anti-PD-1 monotherapy after sorafenib, where Keytruda is an established treatment option for patients,” Scot Ebbinghaus, MD, vice president for clinical research at Merck Research Laboratories, said in a company-issued press release. “It is very encouraging that Keytruda significantly improved overall survival in this study, and we look forward to engaging with regulatory authorities as quickly as possible.”

References:

https://www.healio.com/news/hematology-oncology/20210928/pembrolizumab-extends-os-in-pretreated-hepatocellular-carcinoma