Skip to content

Wolchok JD, et al. Final, 10-Year Outcomes with Nivolumab plus Ipilimumab in Advanced Melanoma. The New England journal of medicine. 2025;392:11-22. PMID 39282897

One-paragraph summary

CheckMate 067 randomised previously untreated patients with advanced melanoma 1:1:1 to nivolumab 1 mg/kg plus ipilimumab 3 mg/kg every 3 weeks for four doses followed by nivolumab 3 mg/kg every 2 weeks; nivolumab 3 mg/kg every 2 weeks plus placebo; or ipilimumab 3 mg/kg every 3 weeks for four doses plus placebo, stratified by BRAF mutation status, metastasis stage and PD-L1 expression, with treatment continued until progression, unacceptable toxicity or withdrawal of consent. At a minimum follow-up of 10 years, median overall survival was 71.9 months with the combination, 36.9 months with nivolumab and 19.9 months with ipilimumab. The hazard ratio for death was 0.53 (95% CI 0.44–0.65) for the combination versus ipilimumab and 0.63 (0.52–0.76) for nivolumab versus ipilimumab. Median melanoma-specific survival exceeded 120 months in the combination arm — not reached, with 37% of patients alive at trial end — against 49.4 months with nivolumab and 21.9 months with ipilimumab (NCT01844505).

Key findings

  • Median overall survival 71.9 / 36.9 / 19.9 months for combination / nivolumab / ipilimumab.
  • Hazard ratio for death 0.53 (0.44–0.65) combination vs ipilimumab; 0.63 (0.52–0.76) nivolumab vs ipilimumab.
  • Median melanoma-specific survival >120 months (not reached) in the combination arm; 37% alive at trial end.
  • Among patients alive and progression-free at 3 years, 10-year melanoma-specific survival was 96% (combination), 97% (nivolumab) and 88% (ipilimumab) — the conditional-survival result that defines what "durable" means in this disease.
  • The 6.5-year analysis of the same trial gave median OS 72.1 / 36.9 / 19.9 months (Wolchok 2022, PMID 34818112), so the curves were essentially flat between 6.5 and 10 years.

Limitations

  • The trial was not powered for a formal combination-versus-monotherapy comparison; that contrast is descriptive (PMID 34818112).
  • Overall survival at 10 years increasingly reflects competing mortality, which is why melanoma-specific survival diverges from overall survival in the final analysis.
  • The population is the 2013–2016 first-line advanced melanoma population: overwhelmingly cutaneous and predominantly White, so the result does not transport to uveal, acral or mucosal disease (see PMID 38048850; PMID 35293617).
  • Treatment continued until progression or toxicity; the trial does not answer how long therapy should be given, which is being tested separately (NCT02821013).
  • No comparison against nivolumab plus relatlimab, the other licensed first-line combination (PMID 34986285).

Why it matters

This is the longest randomised follow-up of checkpoint blockade in any cancer and it converted a hypothesis into a measured quantity: a substantial fraction of patients with advanced melanoma are alive a decade after starting treatment, and among those who reach three years progression-free, melanoma-specific survival at ten years is 96–97%. That conditional-survival figure is what makes melanoma the reference case for durable immunotherapy benefit, and it is the standard against which uveal melanoma's unchanged survival (PMID 40225965) and acral/mucosal melanoma's lower response rates (PMID 40841506) are measured. It also anchors the argument for moving these agents earlier — into the adjuvant and neoadjuvant settings — which is the direction the field has taken (PMID 38828984; PMID 40198940).

Cited by wiki pages

  • immunotherapy in advanced disease
  • overview
  • uveal melanoma
  • epidemiology and global burden
  • clinical trials landscape