According to study data published in the New England Journal of Medicine, 5-year survival was greater in patients with advanced melanoma who received nivolumab plus ipilimumab or nivolumab alone than for patients who received only ipilimumab.
Adult patients with previously untreated stage III or stage IV melanoma were randomly assigned in a 1:1:1 ratio to receive nivolumab (1 mg/kg of body weight) plus ipilimumab (3 mg/kg) every 3 weeks for 4 doses, followed by nivolumab (3 mg/kg) every 2 weeks; or nivolumab (3 mg/kg) every 2 weeks plus ipilimumab-matched placebo; or ipilimumab (3 mg/kg) every 3 weeks for 4 doses plus nivolumab-matched placebo. Primary endpoints were progression-free survival and overall survival at 60 months. Hazard ratios (HRs) for disease progression or death were calculated for each medication regimen. The EQ-5D-3L standardized instrument was used to capture health-related quality of life.
A total of 945 patients were randomly assigned to treatment: 314 to the nivolumab-plus-ipilimumab group, 316 to the nivolumab group, and 315 to the ipilimumab group. Median overall survival was more than 60.0 months (median not reached) in the nivolumab-plus-ipilimumab group, 36.9 months in the nivolumab group, and 19.9 months in the ipilimumab group. Compared with ipilimumab, the HR for death with nivolumab plus ipilimumab was 0.52 (95% CI, 0.42-0.64); for nivolumab alone, the HR was 0.63 (95% CI, 0.52-0.76) (both P <.001). Overall survival at 5 years was 52% in the nivolumab-plus-ipilimumab group, 44% in the nivolumab group, and 26% in the ipilimumab group. The HR for disease progression or death was 0.42 (95% CI, 0.35-0.51; P <.001) for nivolumab plus ipilimumab vs ipilimumab and 0.53 (95% CI, 0.44-0.64; P <.001) for nivolumab vs ipilimumab. No clinically meaningful decrease in health-related quality of life was observed for patients in the nivolumab-plus-ipilimumab and nivolumab treatment groups. Results from safety analyses did not differ from results of prior studies. No previously unreported toxic effects were noted for any treatment group.
Compared with patients who received only ipilimumab, patients given nivolumab or nivolumab plus ipilimumab had greater sustained long-term survival at 5 years. No apparent loss in quality of life was observed in patients receiving nivolumab, and no new safety signals were noted. “This analysis…[shows] that nivolumab-containing regimens were associated with a benefit with respect to overall survival and progression-free survival across patient subgroups,” investigators wrote.
Disclosure: Several study authors declared affiliations with the pharmaceutical industry. Please see the original reference for a full list of authors’ disclosures.
Larkin J, Chiarion-Sileni V, Gonzalez R, et al. Five-year survival with combined nivolumab and ipilimumab in advanced melanoma. N Engl J Med. 2019;381:1535-1546.