Nivolumab plus Ipilimumab for Unresectable Hepatocellular Carcinoma

Immune checkpoint inhibitor–based regimens are standard first-line treatment for unresectable hepatocellular cancer (HCC). Such regimens include bevacizumab plus atezolizumab, tremelimumab plus durvalumab, and now, based on new trial results, nivolumab plus ipilimumab.

CheckMate 9DW was an industry-sponsored, open-label, phase 3 trial in which 668 patients with unresectable HCC were randomized to receive either nivolumab (1 mg/kg) plus ipilimumab (3 mg/kg) every 3 weeks for four treatments, followed by monthly nivolumab (480 mg; IPI/NIVO), or the investigator's choice of either lenvatinib or sorafenib (LS). Patients were predominantly male (82%), with about 40% treated in Asia and another 40% in Europe or North America; 34% had hepatitis B and 28% had hepatitis C.

The key results:

• During a median 3 years' follow-up, the IPI/NIVO group had a median overall survival of 23.7 months compared with 20.6 months in the LS group, a significant difference. The IPI/NIVO group had higher rates of overall survival at both 24 months (49% vs. 39%) and 36 months (38% vs. 24%).
• Early treatment-related deaths occurred in 12 patients receiving IPI/NIVO and 3 receiving LS.
• Median progression-free survival (PFS) was similar in the two groups (approximately 9 months), but the PFS rate at 24 months was higher with IPI/NIVO than with LS (28% vs. 12%).
• Patients receiving IPI/NIVO had a significantly higher response rate than those receiving LS (36% vs. 13%) and a longer median duration of response (30.4 vs. 12.9 months).
• Both groups had about a 40% rate of grade 3/4 treatment-related adverse events.