Adjuvant Therapy of Nivolumab Combined With Ipilimumab Versus Nivolumab Alone in Patients With Resected Stage IIIB-D or Stage IV Melanoma (CheckMate 915)

Author(s): Jeffrey S. Weber, MD, PhD1;Dirk Schadendorf, MD2;Michele Del Vecchio, MD3;James Larkin, PhD, FRCP4;Victoria Atkinson, MD5;Michael Schenker, MD6;Jacopo Pigozzo, MD7;Helen Gogas, MD, PhD8;Stéphane Dalle, MD, PhD9;Nicolas Meyer, MD, PhD10;Paolo A. Ascierto, MD11;Shahneen Sandhu, MBBS12;Thomas Eigentler, MD13;Ralf Gutzmer, MD14;Jessica C. Hassel, MD15;Caroline Robert, MD, PhD16;Matteo S. Carlino, MBBS, PhD17;Anna Maria Di Giacomo, MD, PhD18;Marcus O. Butler, MD19;Eva Muñoz-Couselo, MD20;Michael P. Brown, MBBS, PhD21;Piotr Rutkowski, MD22;Andrew Haydon, MD23;Jean-Jacques Grob, MD24;Jacob Schachter, MD, PhD25;Paola Queirolo, MD26,27;Luis de la Cruz-Merino, MD28;Andre van der Westhuizen, MBChB, MMed29;Alexander M. Menzies, MBBS, PhD30;Sandra Re, MD31;Tuba Bas, PhD31;Veerle de Pril, MSc31;Julia Braverman, PhD31;Daniel J. Tenney, PhD31;Hao Tang, PhD31;and Georgina V. Long, MBBS, PhD30
Source: DOI: 10.1200/JCO.22.00533 Journal of Clinical Oncology 41, no. 3 (January 20, 2023) 517-527
Anjan J Patel MD

Dr. Anjan Patel's Thoughts

More may not always be better.  Adjuvant Nivo q2-weeks + Ipi q6-weeks was not better than Nivo q4 weeks in reducing recurrences in fully resected stage III-IV melanoma.


Ipilimumab and nivolumab have each shown treatment benefit for high-risk resected melanoma. The phase III CheckMate 915 trial evaluated adjuvant nivolumab plus ipilimumab versus nivolumab alone in patients with resected stage IIIB-D or IV melanoma.


In this randomized, double-blind, phase III trial, 1,833 patients received nivolumab 240 mg once every 2 weeks plus ipilimumab 1 mg/kg once every 6 weeks (916 patients) or nivolumab 480 mg once every 4 weeks (917 patients) for ≤ 1 year. After random assignment, patients were stratified by tumor programmed death ligand 1 (PD-L1) expression and stage. Dual primary end points were recurrence-free survival (RFS) in randomly assigned patients and in the tumor PD-L1 expression-level < 1% subgroup.


At a minimum follow-up of approximately 23.7 months, there was no significant difference between treatment groups for RFS in the all-randomly assigned patient population (hazard ratio, 0.92; 95% CI, 0.77 to 1.09; P = .269) or in patients with PD-L1 expression < 1% (hazard ratio, 0.91; 95% CI, 0.73 to 1.14). In all patients, 24-month RFS rates were 64.6% (combination) and 63.2% (nivolumab). Treatment-related grade 3 or 4 adverse events were reported in 32.6% of patients in the combination group and 12.8% in the nivolumab group. Treatment-related deaths were reported in 0.4% of patients in the combination group and in no nivolumab-treated patients.


Nivolumab 240 mg once every 2 weeks plus ipilimumab 1 mg/kg once every 6 weeks did not improve RFS versus nivolumab 480 mg once every 4 weeks in patients with stage IIIB-D or stage IV melanoma. Nivolumab showed efficacy consistent with previous adjuvant studies in a population resembling current practice using American Joint Committee on Cancer eighth edition, reaffirming nivolumab as a standard of care for melanoma adjuvant treatment.

Author Affiliations

1Laura and Isaac Perlmutter Cancer Center, NYU Langone Health, New York, NY; 2Department of Dermatology, University of Essen and the German Cancer Consortium, Partner Site, Essen, Germany; 3Fondazione IRCCS Istituto Nazionale dei Tumori, Milan, Italy; 4The Royal Marsden NHS Foundation Trust, London, United Kingdom; 5Division of Cancer Services, Gallipoli Medical Research Foundation and Princess Alexandra Hospital, University of Queensland, Brisbane, Queensland, Australia; 6Oncology Center Sf Nectarie Ltd, Craiova, Romania; 7Istituto Oncologico Veneto IOV—IRCCS, Padova, Italy; 8National and Kapodistrian University of Athens, Athens, Greece; 9Hospices Civils de Lyon, Lyon, France; 10Institut Universitaire du Cancer and CHU, Toulouse, France; 11Istituto Nazionale Tumori IRCCS Fondazione Pascale, Napoli, Italy; 12Peter MacCallum Cancer Centre and the University of Melbourne, Melbourne, Victoria, Australia; 13Universitätsklinikum und Medizinische Fakultät Tübingen, Tübingen, and Charité—Universitätsmedizin Berlin, corporate member of Freie Universität Berlin and Humboldt Universität zu Berlin, Department of Dermatology, Venerology and Allergology, Berlin, Germany; 14Medizinische Hochschule Hannover, Hannover, and Mühlenkreiskliniken Minden, Ruhr-Universität Bochum, Bochum, Germany; 15Department of Dermatology and National Center for Tumor Diseases, University Hospital Heidelberg, Heidelberg, Germany; 16Gustave Roussy and Paris-Saclay University, Villejuif Cedex, France; 17Westmead and Blacktown Hospitals, University of Sydney, Melanoma Institute Australia, Sydney, New South Wales, Australia; 18Center for Immuno-Oncology, University Hospital of Siena, Siena, Italy; 19Medical Oncology and Hematology, Princess Margaret Cancer Centre, Toronto, Ontario, Canada; 20Vall d’Hebron University, Barcelona, Spain; 21Cancer Trials Unit, Royal Adelaide Hospital, and School of Medicine, The University of Adelaide, Adelaide, Australia; 22Maria Sklodowska-Curie National Institute of Oncology, Warsaw, Poland; 23The Alfred Hospital, Monash University, Melbourne, Australia; 24Department of Dermatology, Aix-Marseille University, Hôpital de la Timone, Marseille, France; 25Sheba Medical Center, IEO European Institute of Oncology, Tel-Hashomer, Israel; 26IEO European Institute of Oncology, IRCCS, Milan, Italy; 27IRCCS San Martino, Genova, Italy; 28Department of Clinical Oncology, Hospital University Virgen Macarena, Seville, Spain; 29Calvary Mater Newcastle Hospital and University of Newcastle. Waratah, New South Wales, Australia; 30Melanoma Institute Australia, University of Sydney, and Royal North Shore and Mater Hospitals, Sydney, New South Wales, Australia; 31Bristol Myers Squibb Company, Princeton, NJ

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