Nivolumab Plus Ipilimumab Shows Promise as First-Line Treatment for Advanced Liver Cancer: CheckMate 9DW

The CheckMate 9DW trial, a large-scale phase 3 study led by Peter Robert Galle, MD, PhD, of the University Medical Center Mainz in Germany, compared the efficacy and safety of nivolumab plus ipilimumab to the current standard treatments of lenvatinib or sorafenib in patients with unresectable hepatocellular carcinoma (uHCC). Results were presented at the 2024 American Society of Clinical Oncology Annual Meeting.

Previously, PD-L1 inhibitors like nivolumab have shown promise in treating uHCC, offering better outcomes than sorafenib. However, the overall prognosis for patients with this aggressive cancer remains poor, highlighting the need for more effective and long-lasting therapies. CheckMate 040 demonstrated the potential of nivolumab plus ipilimumab in patients who had already received sorafenib, leading to its approval in the United States.

The CheckMate 9DW trial enrolled treatment-naive adults with uHCC who were ineligible for curative surgery or other local therapies. Patients were randomized to receive either nivolumab plus ipilimumab followed by maintenance nivolumab, or the investigator’s choice of lenvatinib or sorafenib. The primary end point was overall survival (OS).

After a median follow-up of over 35 months, the trial demonstrated a statistically significant improvement in OS for patients treated with nivolumab plus ipilimumab compared with those receiving lenvatinib or sorafenib. The median OS was 23.7 months for the nivolumab plus ipilimumab group compared with 20.6 months for the lenvatinib/sorafenib group. Additionally, the nivolumab plus ipilimumab arm had a higher percentage of patients still alive at 24 months (49% vs 39%).

The immunotherapy combination also yielded superior results in terms of objective response rate. Thirty-six percent of patients in the nivolumab plus ipilimumab group achieved an objective response compared with 13% in the lenvatinib/sorafenib group. Additionally, responses in the nivolumab plus ipilimumab arm were more durable, with a median duration of response of 30.4 months compared with 12.9 months for lenvatinib/sorafenib.

The safety profile of nivolumab plus ipilimumab was similar to what has been observed in other studies. Treatment-related adverse events were comparable between the 2 groups, with the majority being manageable.

The positive results from CheckMate 9DW suggest that nivolumab plus ipilimumab could become a new standard first-line treatment option for patients with unresectable HCC. This immunotherapy combination offers a statistically significant improvement in OS, higher response rates, and durable responses compared with current standard therapies.