In a 6.5-year update of the phase III CheckMate 067 trial reported in the Journal of Clinical Oncology, Jedd D. Wolchok, MD, PhD, FASCO, and colleagues provided long-term overall survival as well as melanoma-specific survival findings among patients with advanced melanoma who received nivolumab plus ipilimumab, nivolumab, or ipilimumab.
Study Details
In the trial, 945 patients with previously untreated unresectable stage III or stage IV melanoma were randomly assigned 1:1:1 to receive either nivolumab at 1 mg/kg plus four doses of ipilimumab at 3 mg/kg given once every 3 weeks followed by nivolumab at 3 mg/kg once every 2 weeks (n = 314), nivolumab at 3 mg/kg once every 2 weeks (n = 316), or ipilimumab at 3 mg/kg once every 3 weeks for four doses (n = 315). Nivolumab was continued until disease progression or unacceptable toxicity and could be continued beyond progression on the basis of observation of clinical benefit. At 5 years, median overall survival was not reached in the combination group, 36.9 months in the nivolumab group, and 19.9 months in the ipilimumab group; 5-year rates were 52%, 44%, and 26%, respectively.
At the time of the data cutoff (October 2020) for the current analysis, minimum follow-up was 77 months from the date of the first dose of the last patient to be randomly assigned. Hazard ratios are provided as descriptive analyses.
These 6.5-year CheckMate 067 results, which include the longest median overall survival in a phase III melanoma trial reported to date and the first report of melanoma-specific survival, showed durable, improved clinical outcomes with nivolumab plus ipilimumab or nivolumab vs ipilimumab in patients with advanced melanoma and, in descriptive analyses, with the combination over nivolumab monotherapy.— Jedd D. Wolchok, MD, PhD, FASCO, and colleagues
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Key Findings
At minimum follow-up of 6.5 years, median overall survival was 72.1 months (95% confidence interval [CI] = 38.2 months–not reached) in the combination group, 36.9 months (95% CI = 28.2–58.7 months) in the nivolumab group, and 19.9 months (95% CI = 16.8–24.6 months) in the ipilimumab group, with 6.5-year rates of 49%, 42%, and 23%, respectively. Hazard ratios for the combination group vs the nivolumab and ipilimumab groups were 0.84 (95% CI = 0.67–1.04) and 0.52 (95% CI = 0.43–0.64), respectively.
Post-hoc analysis showed that median melanoma-specific survival was not reached (95% CI = 71.9 months–not reached) in the combination group, 58.7 months (95% CI = 35.9 months–not reached) in the nivolumab group, and 21.9 months (95% CI = 18.1–27.4 months) in the ipilimumab group, with 6.5-year rates of 56%, 48%, and 27%, respectively. Hazard ratios for the combination group vs the nivolumab and ipilimumab groups were 0.81 (95% CI = 0.64–1.03) and 0.48 (95% CI = 0.39–0.60), respectively.
Among patients with BRAF-mutant disease, median overall survival was not reached (95% CI = 50.7 months–not reached) in the combination group, 45.5 months (95% CI = 26.4 months–not reached) in the nivolumab group, and 24.6 months (95% CI = 17.9–31.0 months) in the ipilimumab group, with 6.5-year rates of 57%, 43%, and 25%, respectively. Among patients with BRAF wild-type tumors, median overall survival was 39.1 months (95% CI = 27.5 months–not reached), 34.4 months (95% CI = 24.1–59.2 months), and 18.5 months (95% CI = 14.1–22.7 months), respectively; 6.5-year rates were 46%, 42%, and 22%.
No new safety signals were observed since the 5-year analysis.
The investigators concluded, “These 6.5-year CheckMate 067 results, which include the longest median overall survival in a phase III melanoma trial reported to date and the first report of melanoma-specific survival, showed durable, improved clinical outcomes with nivolumab plus ipilimumab or nivolumab vs ipilimumab in patients with advanced melanoma and, in descriptive analyses, with the combination over nivolumab monotherapy.”
Dr. Wolchok, of Memorial Sloan Kettering Cancer Center and Weill Cornell Medical College, is the corresponding author for the Journal of Clinical Oncology article.
Disclosure: The study was supported by grants from the National Cancer Institute and National Institute for Health Research Royal Marsden–Institute of Cancer Research Biomedical Research Centre, and by Bristol Myers Squibb. For full disclosures of the study authors, visit ascopubs.org.
