Drug development for hepatocellular carcinoma

In The Lancet Oncology, Josep M Llovet and colleagues 1 Llovet J Kudo M Merle P et al. Lenvatinib plus pembrolizumab versus lenvatinib plus placebo for advanced hepatocellular carcinoma (LEAP-002): a randomised, double-blind, phase 3 trial. Lancet Oncol. 2023; 24: 1399-1410 Google Scholar report the eagerly awaited results of the LEAP-002 study comparing lenvatinib plus pembrolizumab with lenvatinib plus placebo in advanced hepatocellular carcinoma. 1 Llovet J Kudo M Merle P et al. Lenvatinib plus pembrolizumab versus lenvatinib plus placebo for advanced hepatocellular carcinoma (LEAP-002): a randomised, double-blind, phase 3 trial. Lancet Oncol. 2023; 24: 1399-1410 Google Scholar Despite promising results from the previous phase 1b study of lenvatinib plus pembrolizumab, 2 Finn RS Ikeda M Zhu AX et al. Phase Ib Study of lenvatinib plus pembrolizumab in patients with unresectable hepatocellular carcinoma. J Clin Oncol. 2020; 38: 2960-2970 Crossref PubMed Scopus (655) Google Scholar among 794 patients randomly assigned to lenvatinib plus pembrolizumab (n=395; median age 66·0 years IQR 57–72) or lenvatinib plus placebo (n=399; 66·0 years 57–73; 644 [81%] were male, 150 [19%] were female, 345 [43%] were Asian, 345 [43%] were White, 22 [3%] were multiple races, 21 [3%] were American Indian or Alaska Native, 21 [3%] were Native Hawaiian or other Pacific Islander, and 13 [2%] were Black or African American) the LEAP-002 trial did not meet the prespecified significance for superiority for either of the primary endpoints of progression-free survival and overall survival. Lenvatinib plus pembrolizumab versus lenvatinib plus placebo for advanced hepatocellular carcinoma (LEAP-002): a randomised, double-blind, phase 3 trialIn earlier studies, the addition of pembrolizumab to lenvatinib as first-line therapy for advanced hepatocellular carcinoma has shown promising clinical activity; however, lenvatinib plus pembrolizumab did not meet prespecified significance for improved overall survival and progression-free survival versus lenvatinib plus placebo. Our findings do not support a change in clinical practice. Full-Text PDF