Five-year survival with combined nivolumab and ipilimumab in advanced melanoma: New England Journal of Medicine

J. Larkin, V. Chiarion-Sileni, R. Gonzalez, J.-J. Grob, P. Rutkowski, C.D. Lao, C.L. Cowey, D. Schadendorf, J. Wagstaff, R. Dummer, P.F. Ferrucci, M. Smylie, D. Hogg, A. Hill, I. Márquez-Rodas, J. Haanen, M. Guidoboni, M. Maio, P. Schöffski, M.S. CarlinoC. Lebbé, G. McArthur, P.A. Ascierto, G.A. Daniels, G.V. Long, L. Bastholt, J.I. Rizzo, A. Balogh, A. Moshyk, F.S. Hodi, J.D. Wolchok

Research output: Contribution to journalArticle

Abstract

BACKGROUND Nivolumab plus ipilimumab or nivolumab alone resulted in longer progression-free and overall survival than ipilimumab alone in a trial involving patients with advanced melanoma. We now report 5-year outcomes in the trial. METHODS We randomly assigned patients with previously untreated advanced melanoma to receive one of the following regimens: nivolumab (at a dose of 1 mg per kilogram of body weight) plus ipilimumab (3 mg per kilogram) every 3 weeks for four doses, followed by nivolumab (3 mg per kilogram every 2 weeks); nivolumab (3 mg per kilogram every 2 weeks) plus ipilimumab-matched placebo; or ipilimumab (3 mg per kilogram every 3 weeks for four doses) plus nivolumab-matched placebo. The two primary end points were progression-free survival and overall survival in the nivolumab-plus-ipilimumab group and in the nivolumab group, as compared with the ipilimumab group. RESULTS At a minimum follow-up of 60 months, the median overall survival was more than 60.0 months (median not reached) in the nivolumab-plus-ipilimumab group and 36.9 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, 0.52; hazard ratio for death with nivolumab vs. ipilimumab, 0.63). Overall survival at 5 years was 52% in the nivolumab-plus-ipilimumab group and 44% in the nivolumab group, as compared with 26% in the ipilimumab group. No sustained deterioration of health-related quality of life was observed during or after treatment with nivolumab plus ipilimumab or with nivolumab alone. No new late toxic effects were noted. CONCLUSIONS Among patients with advanced melanoma, sustained long-term overall survival at 5 years was observed in a greater percentage of patients who received nivolumab plus ipilimumab or nivolumab alone than in those who received ipilimumab alone, with no apparent loss of quality of life in the patients who received regimens containing nivolumab. (Funded by Bristol-Myers Squibb and others; CheckMate 067 ClinicalTrials.gov number, NCT01844505.). © 2019 Massachusetts Medical Society.
Original languageEnglish
Pages (from-to)1535-1546
Number of pages12
JournalNew Engl. J. Med.
Volume381
Issue number16
DOIs
Publication statusPublished - 2019

Keywords

  • ipilimumab
  • nivolumab
  • placebo
  • antineoplastic agent
  • B Raf kinase
  • BRAF protein, human
  • advanced cancer
  • Article
  • cancer combination chemotherapy
  • cancer radiotherapy
  • cancer surgery
  • cancer survival
  • controlled study
  • drug response
  • drug safety
  • endocrine disease
  • follow up
  • human
  • long term survival
  • major clinical study
  • melanoma
  • monotherapy
  • overall survival
  • priority journal
  • progression free survival
  • quality of life
  • randomized controlled trial
  • skin disease
  • treatment outcome
  • adult
  • aged
  • clinical trial
  • genetics
  • middle aged
  • mortality
  • multicenter study
  • mutation
  • skin tumor
  • survival analysis
  • Adult
  • Aged
  • Antineoplastic Combined Chemotherapy Protocols
  • Follow-Up Studies
  • Humans
  • Ipilimumab
  • Melanoma
  • Middle Aged
  • Mutation
  • Nivolumab
  • Proto-Oncogene Proteins B-raf
  • Skin Neoplasms
  • Survival Analysis

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    Larkin, J., Chiarion-Sileni, V., Gonzalez, R., Grob, J-J., Rutkowski, P., Lao, C. D., Cowey, C. L., Schadendorf, D., Wagstaff, J., Dummer, R., Ferrucci, P. F., Smylie, M., Hogg, D., Hill, A., Márquez-Rodas, I., Haanen, J., Guidoboni, M., Maio, M., Schöffski, P., ... Wolchok, J. D. (2019). Five-year survival with combined nivolumab and ipilimumab in advanced melanoma: New England Journal of Medicine. New Engl. J. Med., 381(16), 1535-1546. https://doi.org/10.1056/NEJMoa1910836