On 9 November 2018, the FDA granted accelerated approval to pembrolizumab (Keytruda®, Merck) for the treatment of patients with hepatocellular carcinoma (HCC) previously treated with sorafenib.

KEYNOTE-224

The single-arm, multicentre Keynote-224 (NCT02702414) study enrolled 104 HCC patients with measurable disease and a Child-Pugh Class A score whose disease progressed on or after sorafenib and those intolerant to sorafenib. Among the enrolled patients, 21% were hepatitis B virus (HBV) seropositive, 25% were hepatitis C virus (HCV) seropositive, and 9% were both HBV and HCV seropositive. The study excluded patients with underlying autoimmune disease or those with other conditions requiring immunosuppression, as well as patients with more than one aetiology of hepatitis and patients suspect of having ascites by physical examation. Participants received treatment with pembrolizumab untill progression disease, the onset of an unacceptable toxicity, or study completion after 24 months of treatment.

The primary efficacy endpoint was the overall response rate by independent central review (RECIST 1.1) which measured 17% (95% CI, 11-26); 17 partial and one complete response. The duration of response ranged from 3.1 to 16.7 months. The 6-month response rate (RR) was 89% and the 12-month RR was 56%.

Safety

The toxicity profile of pembrolizumab was conform the United States FDA approved product labeling. In this population there were increased incidences of Grade 3/4 ascites (8%) and immune-related hepatitis (2.9%). Grade 3/4 laboratory abnormalities occurring at higher incidence than reported in other KEYNOTE studies included elevated AST (20%), ALT (9%), and hyperbilirubinemia (10%).

Full prescribing information KEYTRUDA®.