Overall Survival with Combined Nivolumab and Ipilimumab in Advanced Melanoma

J. D. Wolchok, V. Chiarion-Sileni, R. Gonzalez, P. Rutkowski, J. J. Grob, C. L. Cowey, C. D. Lao, J. Wagstaff, D. Schadendorf, P. F. Ferrucci, M. Smylie, R. Dummer, A. Hill, D. Hogg, J. Haanen, M. S. Carlino, O. Bechter, M. Maio, I. Marquez-Rodas, M. GuidoboniG. McArthur, C. Lebbé, P. A. Ascierto, G. V. Long, J. Cebon, J. Sosman, M. A. Postow, M. K. Callahan, D. Walker, L. Rollin, R. Bhore, F. S. Hodi, J. Larkin

Research output: Contribution to journalArticle

Abstract

BACKGROUND: Nivolumab combined with ipilimumab resulted in longer progression-free survival and a higher objective response rate than ipilimumab alone in a phase 3 trial involving patients with advanced melanoma. We now report 3-year overall survival outcomes in this trial. METHODS: We randomly assigned, in a 1:1:1 ratio, patients with previously untreated advanced melanoma 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. Randomization was stratified according to programmed death ligand 1 (PD-L1) status, BRAF mutation status, and metastasis stage. The two primary end points were progression-free survival and overall survival in the nivolumab-plus-ipilimumab group and in the nivolumab group versus the ipilimumab group. RESULTS: At a minimum follow-up of 36 months, 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]; hazard ratio for death with nivolumab vs. ipilimumab, 0.65 [P<0.001]). The overall survival rate at 3 years was 58% in the nivolumab-plus-ipilimumab group and 52% in the nivolumab group, as compared with 34% in the ipilimumab group. The safety profile was unchanged from the initial report. Treatment-related adverse events of grade 3 or 4 occurred 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. CONCLUSIONS: 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.

Original languageEnglish
Pages (from-to)1345-1356
Number of pages12
JournalNew England Journal of Medicine
Volume377
Issue number14
DOIs
Publication statusPublished - Oct 5 2017

ASJC Scopus subject areas

  • Medicine(all)

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    Wolchok, J. D., Chiarion-Sileni, V., Gonzalez, R., Rutkowski, P., Grob, J. J., Cowey, C. L., Lao, C. D., Wagstaff, J., Schadendorf, D., Ferrucci, P. F., Smylie, M., Dummer, R., Hill, A., Hogg, D., Haanen, J., Carlino, M. S., Bechter, O., Maio, M., Marquez-Rodas, I., ... Larkin, J. (2017). Overall Survival with Combined Nivolumab and Ipilimumab in Advanced Melanoma. New England Journal of Medicine, 377(14), 1345-1356. https://doi.org/10.1056/NEJMoa1709684