Overall survival with combined nivolumab and ipilimumab in advanced melanoma Journal Article


Authors: 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.; Guidoboni, M.; McArthur, G.; Lebbé, C.; Ascierto, P. A.; Long, G. V.; Cebon, J.; Sosman, J.; Postow, M. A.; Callahan, M. K.; Walker, D.; Rollin, L.; Bhore, R.; Hodi, F. S.; Larkin, J.
Article Title: Overall survival with combined nivolumab and ipilimumab in advanced melanoma
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. Copyright © 2017 Massachusetts Medical Society.
Journal Title: New England Journal of Medicine
Volume: 377
Issue: 14
ISSN: 0028-4793
Publisher: Massachusetts Medical Society  
Date Published: 2017-10-05
Start Page: 1345
End Page: 1356
Language: English
DOI: 10.1056/NEJMoa1709684
PROVIDER: scopus
PUBMED: 28889792
PMCID: PMC5706778
DOI/URL:
Notes: Article -- Export Date: 2 November 2017 -- Source: Scopus
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MSK Authors
  1. Jedd D Wolchok
    771 Wolchok
  2. Michael Andrew Postow
    239 Postow
  3. Margaret Kathleen Callahan
    145 Callahan