Overall Survival With Nivolumab/Ipilimumab, or Nivolumab Alone, vs Ipilimumab in Advanced Melanoma
Overall survival outcomes in the phase III CheckMate 067 trial indicate improved survival with nivolumab (Opdivo)/ipilimumab (Yervoy) vs ipilimumab and with nivolumab vs ipilimumab in patients with previously untreated advanced melanoma. These findings were reported in The New England Journal of Medicine by Wolchok et al.
Study Details
In the double-blind trial, 945 patients with unresectable stage III or IV melanoma from 137 sites in 21 countries were randomized 1:1:1 between July 2013 and March 2014 to receive nivolumab at 1 mg/kg plus ipilimumab at 3 mg/kg every 3 weeks for four doses followed by nivolumab at 3 mg/kg every 2 weeks (n = 314), nivolumab at 3 mg/kg every 2 weeks plus placebo (n = 316), or ipilimumab at 3 mg/kg every 3 weeks for four doses plus placebo (n = 315) until disease progression or unacceptable toxicity. Randomization was stratified by programmed cell death ligand 1 (PD-L1) status, BRAF-mutation status, and metastasis stage. The primary endpoints were progression-free and overall survival in the nivolumab-plus-ipilimumab group and in the nivolumab group vs the ipilimumab group.
An earlier report from the trial showed that progression-free survival was significantly greater with the combination and with nivolumab alone vs ipilimumab alone. The current report is an analysis of 3-year overall survival outcomes.
Overall Survival
At a minimum follow-up of 36 months, median overall survival was not reached in the nivolumab/ipilimumab group (hazard ratio [HR] vs ipilimumab = 0.55, P <.001), 37.6 months in the nivolumab group (HR vs ipilimumab = 0.65, P < .001), and 19.9 months in the ipilimumab group. Overall survival at 3 years was 58%, 52%, and 34%, respectively.
Safety Profile
The safety profile of study treatments was unchanged from the initial report on progression-free survival outcomes. Grade 3 or 4 treatment-related adverse events occurred in 59% of the combination group, 21% of the nivolumab group, and 28% of the ipilimumab group.
The investigators concluded: “Among patients with advanced melanoma, significantly longer overall survival occurred with combination therapy with nivolumab plus ipilimumab or with nivolumab alone than with ipilimumab alone.”
The study was funded by Bristol-Myers Squibb and others.
F. Stephen Hodi, MD, of Dana-Farber Cancer Institute, and James Larkin, FRCP, PhD, of Royal Marsden NHS Foundation Trust, London, contributed equally to The New England Journal of Medicine article.
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