Pembrolizumab Bests Placebo for Second-Line Therapy in Hepatocellular Cancer

Immune checkpoint inhibitors have advanced to first-line treatment for advanced hepatocellular cancer, with recent FDA approval for atezolizumab/bevacizumab and tremelimumab/durvalumab. Single-agent immune checkpoint inhibitors, however, have achieved mixed results in first- or later-line therapy.

Investigators from China now report results of KEYNOTE-394, an industry-sponsored, double-blind, placebo-controlled, randomized, phase 3 trial comparing pembrolizumab to placebo as second-line therapy in advanced hepatocellular cancer. Of 453 patients, median age was 54, most were men, all had Child-Pugh liver classification A, and most had hepatitis B (79%) and extrahepatic disease (78%). Patients had previously received sorafenib (91%) or oxaliplatin-based chemotherapy (9%).

At a median follow-up of 33.8 months, overall survival (OS), the primary endpoint, was superior for pembrolizumab compared to placebo (median, 14.6 vs. 13.0 months; hazard ratio, 0.79; P=0.0180), with higher overall survival at 24 months (34.3% vs. 24.9%) and 36 months (23.4% vs. 11.0%). Progression-free survival (PFS) was also superior for pembrolizumab (median, 2.6 vs. 2.3 months; HR, 0.74; P=0.0032), with greater PFS at 12 months (15.9% vs. 1.4%) and 18 months (11.8% vs. 0%). Response to therapy was higher with pembrolizumab (12.7% vs. 1.3%). No new safety signals were observed.