Final results from the Phase III CheckMate -067 trial demonstrate that the combination of Opdivo (nivolumab) and Yervoy (ipilimumab) provides a significant and durable survival benefit for patients with previously untreated advanced or metastatic melanoma. The 10-year follow-up data, published in The New England Journal of Medicine, represent the longest reported median overall survival (OS) data for a Phase III advanced melanoma trial.
The CheckMate -067 trial compared the Opdivo plus Yervoy combination to Opdivo monotherapy and Yervoy monotherapy in 945 patients who had not received prior treatment for advanced melanoma. Patients in the combination arm received Opdivo 1 mg/kg plus Yervoy 3 mg/kg every three weeks for four doses, followed by Opdivo 3 mg/kg every two weeks. The primary endpoints were OS and progression-free survival.
Landmark Survival Data
At a minimum follow-up of 10 years, the median OS was 71.9 months in the Opdivo plus Yervoy arm, compared to 36.9 months in the Opdivo monotherapy arm and 19.9 months in the Yervoy monotherapy arm. The hazard ratio for death was 0.53 (95% CI, 0.44 to 0.65) for the combination versus Yervoy monotherapy, and 0.63 (95% CI, 0.52 to 0.76) for Opdivo monotherapy versus Yervoy monotherapy.
Median melanoma-specific survival was more than 120 months in the Opdivo plus Yervoy cohort (37% of patients alive at the end of the trial), compared to 49.4 months with Opdivo monotherapy and 21.9 months with Yervoy monotherapy. Among patients alive and progression-free at three years, 10-year melanoma-specific survival was 96% in the Opdivo plus Yervoy cohort, 97% with Opdivo monotherapy, and 88% with Yervoy monotherapy.
Clinical Impact and Expert Commentary
"These data continue to demonstrate the impressive and durable clinical benefit of nivolumab in combination with ipilimumab with survival curves remaining stable for some years now," said James Larkin, PhD, FRCP, consultant medical oncologist at The Royal Marsden. "Remarkably, 43% of patients treated with Opdivo and Yervoy are alive ten years later and many did not need subsequent therapy."
The objective response rate (ORR) after 10 years was 58.3% in the Opdivo plus Yervoy arm, 44.9% in the Opdivo monotherapy arm, and 9.0% in the Yervoy monotherapy arm.
Safety Profile
The safety profile of the Opdivo plus Yervoy combination was consistent with previous reports. Grade 3/4 treatment-related adverse events were reported in 62.6% of patients in the combination arm, 24.6% in the Opdivo monotherapy arm, and 29.6% in the Yervoy monotherapy arm. No new safety signals were identified.
Implications for Advanced Melanoma Treatment
"As compared with ipilimumab monotherapy, nivolumab-containing therapies have continued to show a prolonged survival benefit in patients with advanced melanoma, with no new safety signals," the study authors concluded. "These 10-year data underscore how immune checkpoint inhibitor therapy has helped to change the long-term prognosis for patients with advanced melanoma and highlight the potential for a cure in patients who have a response to this type of treatment."
