Overall Survival with Combined Nivolumab and Ipilimumab in Advanced Melanoma.
Level 2 - randomized trial
Phase 3 randomized controlled trial
PubMed 28889792 · doi:10.1056/NEJMoa1709684
What was done
Patients with previously untreated advanced melanoma were randomly assigned in a 1:1:1 ratio to receive 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 until disease progression, unacceptable toxicity, or consent withdrawal. Randomization was stratified by PD-L1 status, BRAF mutation status, and metastasis stage. The primary end points were progression-free survival and overall survival evaluated at a minimum follow-up of 36 months.
What was found
Median overall survival was not reached with nivolumab plus ipilimumab and was 37.6 months with nivolumab alone, compared with 19.9 months with ipilimumab alone. The hazard ratio for death versus ipilimumab was 0.55 (P<0.001) for combination therapy and 0.65 (P<0.001) for nivolumab monotherapy. The 3-year overall survival rate was 58% for nivolumab plus ipilimumab, 52% for nivolumab alone, and 34% for ipilimumab alone. Grade 3 or 4 treatment-related adverse events occurred in 59% of patients on combination therapy, 21% on nivolumab alone, and 28% on ipilimumab alone.
Why it matters
Combination nivolumab and ipilimumab, as well as nivolumab monotherapy, provide substantial and durable 3-year overall survival benefits over ipilimumab monotherapy in untreated advanced melanoma.
Limits
The abstract does not state total participant numbers or provide statistical comparisons directly comparing nivolumab plus ipilimumab against nivolumab monotherapy. Grade 3 or 4 treatment-related adverse events were high in the combination arm (59%).
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