Pembrolizumab As Second-line Therapy In Patients With Advanced Hepatocellular Carcinoma In Keynote-240: A Randomized, Double-blind, Phase Iii Trial.
This is the report of a phase 3 study assessing efficacy and safety of pembrolizumab in patients with advanced hepatocellular carcinoma (HCC) previously treated with sorafenib. 413 patients were randomized 2:1 to receive pembrolizumab or placebo. Median overall survival (OS) was 13.9 months for pembrolizumab vs 10.6 months for placebo (hazard ratio [HR] 0.781; 95%CI 0.611-0.998; P=0.0238). Median progression-free survival (PFS) was 3.0 months for pembrolizumab vs 2.8 months for placebo at the first interim analysis (HR 0.775; 95%CI 0.609-0.987; P=0.0186) and 3.0 months vs 2.8 months at final analysis (HR 0.718; 95%CI 0.570-0.904; P=0.0022). Grade ≥3 adverse events (AEs) occurred in 147 (52.7%) and 62 patients (46.3%) for pembrolizumab versus placebo; grade ≥3 treatment-related AEs in 52 (18.6%) and 10 patients (7.5%), respectively; no hepatitis C or B flares were observed. Although this trial is negative, the results are consistent with the previous KEYNOTE-224 phase 2 study, supporting a favorable risk-to-benefit ratio for pembrolizumab in this population.