ONCOmmunity

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

By: Jedd D Wolchok, Vanna Chiarion-Sileni, Piotr Rutkowski, C Lance Cowey, Dirk Schadendorf, John Wagstaff, Paola Queirolo, Reinhard Dummer, Marcus O Butler, Andrew G Hill, Michael A Postow, Caroline Gaudy-Marqueste, Theresa Medina, Christopher D Lao, John Walker, Iván Márquez-Rodas, John B A G Haanen, Massimo Guidoboni, Michele Maio, Patrick Schöffski, Matteo S Carlino, Shahneen Sandhu, Céleste Lebbé, Paolo A Ascierto, Georgina V Long, Corey Ritchings, Ayman Nassar, Margarita Askelson, Melanie Pe Benito, Wenjia Wang, F Stephen Hodi, James Larkin,

From the Sandra and Edward Meyer Cancer Center (J.D.W.) and the Department of Medicine (J.D.W., M.A.P.), Weill Cornell Medicine, and Memorial Sloan Kettering Cancer Center (M.A.P.) - both in New York; Istituto Oncologico Veneto, IRCCS, Padua (V.C.-S.), European Institute of Oncology, IRCCS, Milan (P.Q.), Istituto Scientifico Romagnolo per lo Studio e la Cura dei Tumori, IRCCS, Meldola (M.G.), University of Siena and the Center for Immuno-Oncology, University Hospital of Siena, Siena (M.M.), and Istituto Nazionale Tumori IRCCS Fondazione Pascale, Naples (P.A.A.) - all in Italy; Maria Sklodowska-Curie National Institute of Oncology, Warsaw, Poland (P.R.); Texas Oncology-Baylor Charles A. Sammons Cancer Center, Dallas (C.L.C.); University Hospital Essen, the German Cancer Consortium, the National Center for Tumor Diseases-West, the Research Alliance Ruhr, Research Center One Health, and University Duisburg-Essen - all in Essen, Germany (D.S.); the College of Medicine, Swansea University, Swansea (J.W.), Bristol Myers Squibb, Uxbridge (A.N.), and the Royal Marsden Hospital, London (J.L.) - all in the United Kingdom; the Department of Dermatology, University of Zurich, Zurich, Switzerland (R.D.); University Health Network Princess Margaret Cancer Centre, Toronto (M.O.B.), and Cross Cancer Institute, University of Alberta, Edmonton (J.W.) - both in Canada; Tasman Oncology Research, Southport, QLD (A.G.H.), Westmead Hospital, Westmead, NSW (M.S.C.), Blacktown Hospital, Blacktown, NSW (M.S.C.), the Melanoma Institute Australia, University of Sydney (M.S.C., G.V.L.), Royal North Shore Hospital (G.V.L.), and Mater Hospital (G.V.L.), Sydney, and Peter MacCallum Cancer Centre, University of Melbourne, Melbourne, VIC (S.S.) - all in Australia; Aix-Marseille Université, Assistance Publique-Hôpitaux de Marseille, Marseille (C.G.-M.), and Université Paris Cité, Assistance Publique-Hôpitaux de Paris (AP-HP) Dermato-oncology, Clinical Investigation Center, the Cancer Institute, AP-HP Nord Paris Cité, INSERM Unité 976, and St. Louis Hospital, Paris (C.L.) - all in France; the University of Colorado Cancer Center, Aurora (T.M.); Rogel Cancer Center, University of Michigan, Ann Arbor (C.D.L.); Hospital General Universitario Gregorio Marañon, Madrid (I.M-R.); the Netherlands Cancer Institute, Amsterdam (J.B.A.G.H.); University Hospital Leuven and Leuven Cancer Institute, KU Leuven, Leuven, Belgium (P.S.); Bristol Myers Squibb, Princeton, NJ (C.R., M.A., M.P.B., W.W.); and Dana-Farber Cancer Institute, Boston (F.S.H.).
2024-9-17; 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.).