Final, 10-Year Outcomes with Nivolumab plus Ipilimumab in Advanced Melanoma.
Level 2 - randomized trial
Phase III randomized controlled trial
PubMed 39282897 · doi:10.1056/NEJMoa2407417
What was done
Patients with previously untreated advanced melanoma were randomly assigned (1:1:1) to one of three regimens: 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. Randomization was stratified by BRAF mutation status, metastasis stage, and programmed death ligand 1 (PD-L1) expression. Treatment continued until disease progression, unacceptable toxicity, or withdrawal of consent. The trial evaluated 10-year overall survival, melanoma-specific survival, and response durability.
What was found
At a minimum follow-up of 10 years, median overall survival was 71.9 months with nivolumab plus ipilimumab, 36.9 months with nivolumab monotherapy, and 19.9 months with ipilimumab monotherapy. Compared with ipilimumab, the hazard ratio for death was 0.53 (95% CI, 0.44 to 0.65) for nivolumab plus ipilimumab and 0.63 (95% CI, 0.52 to 0.76) for nivolumab alone. Median melanoma-specific survival was >120 months (not reached, with 37% alive at trial end) for nivolumab plus ipilimumab, 49.4 months for nivolumab, and 21.9 months for ipilimumab. Among patients alive and progression-free at 3 years, 10-year melanoma-specific survival was 96% with nivolumab plus ipilimumab, 97% with nivolumab, and 88% with ipilimumab.
Why it matters
This 10-year follow-up confirms durable, long-term survival benefits for checkpoint inhibitor regimens in advanced melanoma, showing that more than a third of patients receiving combination immunotherapy achieve decade-long melanoma-specific survival.
Limits
The total sample size (n) and subgroup patient counts are not reported in the abstract. The abstract does not provide data on long-term safety, late-onset immune-related adverse events, or subsequent post-progression therapies received during the 10-year period.