Multinational phase 3 trial of first-line nivolumab plus ipilimumab versus lenvatinib or sorafenib for unresectable hepatocellular carcinoma

The multinational phase 3 CheckMate 9DW trial compared first-line nivolumab plus ipilimumab versus investigator’s choice of lenvatinib or sorafenib for previously untreated unresectable hepatocellular carcinoma (uHCC). Primary endpoint was overall survival, which was worse with nivolumab-ipilimumab during the first 6 months after randomisation (HR 1.65; 95% CI 1.12-1.43) followed by a sustained separation of the curves thereafter in favor of nivolumab-ipilimumab (0.61; 0.48-0.77), resulting in a signifcantly improved OS with nivolumab-ipilimumab after a median follow-up of 35.2 months (median 23.7 months versus 20.6 months; p=0.018). Grade 3 or 4 TRAEs were reported for 41% of patients with nivolumab-ipilimumab and 42% of patients with lenvatinib or sorafenib. The authors conclude that nivolumab plus ipilimumab showed a significant overall survival benefit versus lenvatinib or sorafenib with manageable safety in patients with previously untreated uHCC.