Drug development for hepatocellular carcinoma

• Published in: The lancet oncology Vol. 24; no. 12; pp. 1292 - 1294
• Main Authors: Chan, Landon L, Chan, Stephen L
• Format: Journal Article
• Language: English
• Published: England Elsevier Ltd 01.12.2023; Elsevier Limited
• Subjects: Antibodies; Carcinoma, Hepatocellular - drug therapy; Carcinoma, Hepatocellular - pathology; Clinical trials; Drug Development; Hepatitis; Hepatocellular carcinoma; Humans; Immunotherapy; Liver cancer; Liver Neoplasms - drug therapy; Liver Neoplasms - pathology; Monoclonal antibodies; PD-1 protein; PD-L1 protein; Pembrolizumab; Survival; Targeted cancer therapy
• ISSN: 1470-2045; 1474-5488; 1474-5488
• DOI: 10.1016/S1470-2045(23)00523-5

In this study, the median overall survival of 19·0 months in the lenvatinib group is remarkably longer than the median overall survival of 13·6 months in the previous phase 3 non-inferiority study comparing lenvatinib with sorafenib.6 As a result, the investigators of LEAP-002 underestimated the performance of the control group, and so the study was underpowered to detect a difference from the combination regimen. Subgroup analyses of clinical trials on monotherapy anti-PD-1 have reported a trend of increased benefits in patients with viral hepatitis, but these results have been challenged by a meta-analysis that included clinical trials investigating the combination of anti-PD-1 or anti-PD-L1 antibodies and other agents.9,10 A prespecified subgroup analysis of LEAP-002 provides support to the latter observation by finding no difference in the estimates for overall survival between patients with and without viral hepatitis.1 However, the representation of aetiological subgroups varies remarkably among different clinical trials. [...]we congratulate the LEAP-002 investigators for completing this international study, which provides important clinical data on the combination of lenvatinib plus pembrolizumab in advanced hepatocellular carcinoma.