Pembrolizumab Added to Lenvatinib for Patients with Hepatocellular Carcinoma?

First-line therapy with lenvatinib or sorafenib for patients with advanced hepatocellular cancer (HCC) has been replaced by immunotherapy-based combinations. These investigators report results of the LEAP-002 trial, an industry-sponsored, randomized trial comparing lenvatinib with or without pembrolizumab in patients with advanced HCC.

The 794 patients received oral lenvatinib daily (8 or 12 mg/kg, depending on bodyweight), combined with intravenous pembrolizumab (200 mg) or placebo every 3 weeks. Overall, 49% tested positive for hepatitis B and 23% tested positive for hepatitis C; 32% had liver disease related to alcohol, and 62% had extrahepatic disease. At a median of 32 months from randomization to the final data cutoff, the coprimary endpoint of superiority for overall survival with pembrolizumab was not reached and did not cross the superiority boundary, with a median overall survival of 21.2 months for the pembrolizumab group and 19.0 months for the placebo group. The other primary endpoint, median progression-free survival, was similar for patients taking pembrolizumab (8.2 months) and those taking placebo (8.0 months), which did not cross the superiority boundary. Serious treatment-related adverse events occurred in 25% of the pembrolizumab recipients and 16% of the placebo recipients.