Final, 10-Year Outcomes with Nivolumab plus Ipilimumab in Advanced Melanoma.

Wolchok JD, Chiarion-Sileni V, Rutkowski P, Cowey CL, Schadendorf D, Wagstaff J, Queirolo P, Dummer R, Butler MO, Hill AG, Postow MA, Gaudy-Marqueste C, Medina T, Lao CD, Walker J, Márquez-Rodas I, Haanen JB, Guidoboni M, Maio M, Schöffski P, Carlino MS, Sandhu S, Lebbé C, Ascierto PA, Long GV, Ritchings C, Nassar A, Askelson M, Benito MP, Wang W, Hodi FS, Larkin J (2025)

Publication Type: Journal article

Publication year: 2025

Journal

Book Volume: 392

Pages Range: 11-22

Journal Issue: 1

DOI: 10.1056/NEJMoa2407417

Abstract

BACKGROUND: Previous results from this trial showed longer overall survival after treatment with nivolumab plus ipilimumab or with nivolumab monotherapy than with ipilimumab monotherapy in patients with advanced melanoma. Given that patients with advanced melanoma are living longer than 7.5 years, longer-term data were needed to address new clinically relevant questions. METHODS: We randomly assigned patients with previously untreated advanced melanoma, in a 1:1:1 ratio, to one of the following regimens: nivolumab (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 placebo; or ipilimumab (3 mg per kilogram) every 3 weeks for four doses plus placebo. Treatment was continued until the occurrence of disease progression, unacceptable toxic effects, or withdrawal of consent. Randomization was stratified according to BRAF mutation status, metastasis stage, and programmed death ligand 1 expression. Here, we report the final, 10-year results of this trial, including results for overall survival and melanoma-specific survival, as well as durability of response. RESULTS: With a minimum follow-up of 10 years, median overall survival was 71.9 months with nivolumab plus ipilimumab, 36.9 months with nivolumab, and 19.9 months with ipilimumab. The hazard ratio for death was 0.53 (95% confidence interval [CI], 0.44 to 0.65) for nivolumab plus ipilimumab as compared with ipilimumab and was 0.63 (95% CI, 0.52 to 0.76) for nivolumab as compared with ipilimumab. Median melanoma-specific survival was more than 120 months with nivolumab plus ipilimumab (not reached, with 37% of the patients alive at the end of the trial), 49.4 months with nivolumab, and 21.9 months with ipilimumab. Among patients who had been alive and progression-free at 3 years, 10-year melanoma-specific survival was 96% with nivolumab plus ipilimumab, 97% with nivolumab, and 88% with ipilimumab. CONCLUSIONS: The final trial results showed a continued, ongoing survival benefit with nivolumab plus ipilimumab and with nivolumab monotherapy, as compared with ipilimumab monotherapy, in patients with advanced melanoma. (Funded by Bristol Myers Squibb and others; CheckMate 067 ClinicalTrials.gov number, NCT01844505.).

Involved external institutions

Weill Cornell Medicine United States (USA) (US) Istituto Oncologico Veneto (IOV), IRCCS Italy (IT) Maria Skłodowska-Curie Institute of Oncology / Centrum Onkologii–Instytut im. Marii Skłodowskiej-Curie w Warszawie Poland (PL) Texas Oncology United States (USA) (US) Universitätsklinikum Essen Germany (DE) Swansea University United Kingdom (GB) European Institute of Oncology / Istituto Europeo di Oncologia (IEO) Italy (IT) University of Zurich / Universität Zürich (UZH) Switzerland (CH) Princess Margaret Cancer Centre / Princess Margaret Hospital Canada (CA) Aix-Marseille University / Aix-Marseille Université France (FR) University of Colorado Cancer Center United States (USA) (US) University of Michigan United States (USA) (US) Hospital General Universitario Gregorio Marañón Spain (ES) Netherlands Cancer Institute - Antoni van Leeuwenhoek Hospital (NKI / NKI-AVL) Netherlands (NL) Istituto Romagnolo per lo Studio dei Tumori "Dino Amadori" (IRST) Italy (IT) Università degli Studi di Siena (UNISI) / University of Siena Italy (IT) University Hospital Leuven (UZ) / Universitaire ziekenhuizen Leuven Belgium (BE) Westmead Hospital Australia (AU) The University of Melbourne Australia (AU) Bristol-Myers Squibb United States (USA) (US) Dana–Farber Cancer Institute United States (USA) (US) Royal Marsden Hospital / The Royal Marsden NHS Foundation Trust United Kingdom (GB) Université Sorbonne Paris Cité France (FR) Istituto Nazionale Tumori IRCCS "Fondazione G. Pascale" Italy (IT) University of Sydney (USYD) Australia (AU)

How to cite

APA:

Wolchok, J.D., Chiarion-Sileni, V., Rutkowski, P., Cowey, C.L., Schadendorf, D., Wagstaff, J.,... Larkin, J. (2025). Final, 10-Year Outcomes with Nivolumab plus Ipilimumab in Advanced Melanoma. New England Journal of Medicine, 392(1), 11-22. https://doi.org/10.1056/NEJMoa2407417

MLA:

Wolchok, Jedd D., et al. "Final, 10-Year Outcomes with Nivolumab plus Ipilimumab in Advanced Melanoma." New England Journal of Medicine 392.1 (2025): 11-22.

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