TOPLINE:

Nivolumab plus ipilimumab (NIPO + IPI) showed sustained survival benefit vs lenvatinib or sorafenib for patients with unresectable hepatocellular carcinoma (HCC), with 4-year overall survival rates of 31% vs 18%.

METHODOLOGY:

• Based on the initial results of CheckMate 9DW, NIVO + IPI is approved in numerous countries as first-line treatment for patients with unresectable HCC. At a pre-planned interim analysis, with 35 months of follow-up, the immunotherapy duo showed a significant overall survival benefit compared with lenvatinib or sorafenib (hazard ratio [HR], 0.79; 95% CI, 0.65-0.96). Longer-term follow-up was ongoing.
• CheckMate 9DW involved 668 patients with previously untreated advanced HCC who were randomly assigned to receive either NIVO 1 mg/kg + IPI 3 mg/kg every 3 weeks for up to four cycles followed by NIVO 480 mg every 4 weeks, or investigator’s choice of lenvatinib (8 mg or 12 mg daily) or sorafenib (400 mg twice daily). Treatment with NIVO continued for a maximum of 2 years or until disease progression or unacceptable toxicity.
• Overall survival was the primary endpoint, with objective response rate and duration of response as secondary endpoints.

TAKEAWAY:

• At a median follow-up of 52.5 months, NIVO + IPI demonstrated continued overall survival benefit (HR, 0.78; 95% Cl, 0.65-0.93). The 4-year overall survival rate was 31% with the immunotherapy combination compared with 18% with lenvatinib/sorafenib.
• Patients receiving NIVO + IPI also had a higher objective response rate (36% vs 13%) and longer median duration of response (34.3 months vs 12.9 months).
• Side effects were consistent with the previous analysis, with no new safety signals. Treatment-related adverse events were seen in 83% and 91% of patients in the NIVO + IPI and lenvatinib/sorafenib arms, respectively, with grade 3 or 4 events in 41% and 42%, respectively. The most common adverse events with NIVO + IPI included pruritus, rash, increased liver enzymes, diarrhea, and hypothyroidism.
• Among NIVO + IPI patients, 63 (19%) developed immune-mediated hepatitis, mostly grade 3 or 4 and usually managed with high-dose steroids. Those events resolved in 47 of the 63 patients (75%).

IN PRACTICE:

“After 4 years of follow-up, first-line NIVO + IPI continued to show sustained efficacy benefit vs lenvatinib/sorafenib in unresectable HCC and manageable safety with no new concerns,” the study authors reported. “These results continue to support NIVO + IPI as a standard-of-care treatment in these patients.”

SOURCE:

The study, led by Peter R. Galle, MD, PhD, University Medical Center in Mainz, Germany, was presented at the ASCO Gastrointestinal Cancers Symposium 2026.

LIMITATIONS:

Limitations of the trial included the exclusion of patients with Vp4 portal vein thrombosis and the open-label design.

DISCLOSURES:

The study was funded by Bristol Myers Squibb. Galle and several co-authors disclosed financial relationships with Bristol Myers Squibb and various other sources.

This article was created using several editorial tools, including AI, as part of the process. Human editors reviewed this content before publication.