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

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.

PURPOSE

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.

PATIENTS AND METHODS

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.

RESULTS

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.

CONCLUSION

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

Leave a Comment

Your email address will not be published. Required fields are marked *

Related Articles

Neoadjuvant Nivolumab and Ipilimumab in Resectable Stage III Melanoma

This was compared to adjuvant niovolumab for 12 months, patients who did not achieve complete response also received adjuvant nivo. Neoadjuvant therapy was for 2 cycles. 12-month event-free survival was 83.7% in the neoadjuvant group and 57.2% in the adjuvant group. 58% had major pathological response in the neoadjuvant group, less than 5% could not get the surgery. The estimated 12-month recurrence-free survival was 95.1% in patients in the neoadjuvant group who had a major pathological response, 76.1% among those with a partial response, and 57.0% among those with a nonresponse.

Read More »

Neoadjuvant–Adjuvant or Adjuvant-Only Pembrolizumab in Advanced Melanoma

Interesting study showing a strong difference in EFS with neoadjuvant + adjuvant vs. adjuvant alone for stage III/IV melanoma. All patients had disease that was amenable to surgery; EFS at 24 months was 72% vs. 49% in favor of the neoadjuvant group. The hypothesis is that neoadjuvant therapy functionally inhibits the immune checkpoint before antitumor T-cells are surgically resected. This concept is also developing in other cancers, including NSCLC, breast and bladder cancers. This should affect clinical practice.

Read More »