Wolchok JD, et al. - This study sought to report 3-year overall survival outcomes with combined nivolumab and ipilimumab in the phase 3 trial involving patients with advanced melanoma. Among these patients, researchers noticed significantly longer overall survival with combination therapy with nivolumab plus ipilimumab or with nivolumab alone than with ipilimumab alone.

Methods

• In a 1:1:1 ratio, patients with previously untreated advanced melanoma were randomly assigned to receive nivolumab at a dose of 1 mg per kilogram of body weight plus ipilimumab at a dose of 3 mg per kilogram every 3 weeks for four doses, followed by nivolumab at a dose of 3 mg per kilogram every 2 weeks; nivolumab at a dose of 3 mg per kilogram every 2 weeks plus placebo; or ipilimumab at a dose of 3 mg per kilogram every 3 weeks for four doses plus placebo, until progression, the occurrence of unacceptable toxic effects, or withdrawal of consent.
• In accordance to programmed death ligand 1 (PD-L1) status, BRAF mutation status, and metastasis stage, randomization was stratified.
• Progression-free survival and overall survival in the nivolumab-plus-ipilimumab group and in the nivolumab group versus the ipilimumab group were assessed as the two primary end points.

Results

• The median overall survival had not been reached in the nivolumab-plus-ipilimumab group and was 37.6 months in the nivolumab group, as compared with 19.9 months in the ipilimumab group (hazard ratio for death with nivolumab plus ipilimumab vs. ipilimumab, 0.55 [P<0.001] at a minimum follow-up of 36 months; for death with nivolumab vs. ipilimumab, hazard ratio was 0.65 [P<0.001]).
• At 3 years, nivolumab-plus-ipilimumab group and the nivolumab group had the overall survival rate of 58% and 52%, respectively, as compared with 34% in the ipilimumab group.
• The safety profile was in accordance with the initial report.
• Treatment-related adverse events of grade 3 or 4 were encountered in 59% of the patients in the nivolumab-plus-ipilimumab group, in 21% of those in the nivolumab group, and in 28% of those in the ipilimumab group.