Adjuvant Therapy of Nivolumab Combined With Ipilimumab Versus Nivolumab Alone in Patients With Resected Stage IIIB-D or Stage IV Melanoma (CheckMate 915)-Reference-Cited by-同舟云学术

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

Published:2023-01-20 Issue:3 Volume:41 Page:517-527
ISSN:0732-183X
Container-title:Journal of Clinical Oncology
language:en
Short-container-title:JCO

Author:

Weber Jeffrey S.¹^ORCID,Schadendorf Dirk²^ORCID,Del Vecchio Michele³,Larkin James⁴^ORCID,Atkinson Victoria⁵,Schenker Michael⁶^ORCID,Pigozzo Jacopo⁷^ORCID,Gogas Helen⁸^ORCID,Dalle Stéphane⁹,Meyer Nicolas¹⁰,Ascierto Paolo A.¹¹^ORCID,Sandhu Shahneen¹²^ORCID,Eigentler Thomas¹³,Gutzmer Ralf¹⁴^ORCID,Hassel Jessica C.¹⁵^ORCID,Robert Caroline¹⁶^ORCID,Carlino Matteo S.¹⁷,Di Giacomo Anna Maria¹⁸,Butler Marcus O.¹⁹^ORCID,Muñoz-Couselo Eva²⁰^ORCID,Brown Michael P.²¹^ORCID,Rutkowski Piotr²²^ORCID,Haydon Andrew²³^ORCID,Grob Jean-Jacques²⁴^ORCID,Schachter Jacob²⁵,Queirolo Paola²⁶²⁷,de la Cruz-Merino Luis²⁸^ORCID,van der Westhuizen Andre²⁹^ORCID,Menzies Alexander M.³⁰^ORCID,Re Sandra³¹,Bas Tuba³¹,de Pril Veerle³¹,Braverman Julia³¹,Tenney Daniel J.³¹^ORCID,Tang Hao³¹,Long Georgina V.³⁰^ORCID

Affiliation:

1. Laura and Isaac Perlmutter Cancer Center, NYU Langone Health, New York, NY

2. Department of Dermatology, University of Essen and the German Cancer Consortium, Partner Site, Essen, Germany

3. Fondazione IRCCS Istituto Nazionale dei Tumori, Milan, Italy

4. The Royal Marsden NHS Foundation Trust, London, United Kingdom

5. Division of Cancer Services, Gallipoli Medical Research Foundation and Princess Alexandra Hospital, University of Queensland, Brisbane, Queensland, Australia

6. Oncology Center Sf Nectarie Ltd, Craiova, Romania

7. Istituto Oncologico Veneto IOV—IRCCS, Padova, Italy

8. National and Kapodistrian University of Athens, Athens, Greece

9. Hospices Civils de Lyon, Lyon, France

10. Institut Universitaire du Cancer and CHU, Toulouse, France

11. Istituto Nazionale Tumori IRCCS Fondazione Pascale, Napoli, Italy

12. Peter MacCallum Cancer Centre and the University of Melbourne, Melbourne, Victoria, Australia

13. Universitätsklinikum 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

14. Medizinische Hochschule Hannover, Hannover, and Mühlenkreiskliniken Minden, Ruhr-Universität Bochum, Bochum, Germany

15. Department of Dermatology and National Center for Tumor Diseases, University Hospital Heidelberg, Heidelberg, Germany

16. Gustave Roussy and Paris-Saclay University, Villejuif Cedex, France

17. Westmead and Blacktown Hospitals, University of Sydney, Melanoma Institute Australia, Sydney, New South Wales, Australia

18. Center for Immuno-Oncology, University Hospital of Siena, Siena, Italy

19. Medical Oncology and Hematology, Princess Margaret Cancer Centre, Toronto, Ontario, Canada

20. Vall d'Hebron University, Barcelona, Spain

21. Cancer Trials Unit, Royal Adelaide Hospital, and School of Medicine, The University of Adelaide, Adelaide, Australia

22. Maria Sklodowska-Curie National Institute of Oncology, Warsaw, Poland

23. The Alfred Hospital, Monash University, Melbourne, Australia

24. Department of Dermatology, Aix-Marseille University, Hôpital de la Timone, Marseille, France

25. Sheba Medical Center, IEO European Institute of Oncology, Tel-Hashomer, Israel

26. IEO European Institute of Oncology, IRCCS, Milan, Italy

27. IRCCS San Martino, Genova, Italy

28. Department of Clinical Oncology, Hospital University Virgen Macarena, Seville, Spain

29. Calvary Mater Newcastle Hospital and University of Newcastle. Waratah, New South Wales, Australia

30. Melanoma Institute Australia, University of Sydney, and Royal North Shore and Mater Hospitals, Sydney, New South Wales, Australia

31. Bristol Myers Squibb Company, Princeton, NJ

Abstract

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.

Publisher

American Society of Clinical Oncology (ASCO)

Subject

Cancer Research,Oncology

Link

https://ascopubs.org/doi/pdfdirect/10.1200/JCO.22.00533

Reference28 articles.

1. Prolonged Survival in Stage III Melanoma with Ipilimumab Adjuvant Therapy

2. Adjuvant Nivolumab versus Ipilimumab in Resected Stage III or IV Melanoma

3. Adjuvant Pembrolizumab versus Placebo in Resected Stage III Melanoma

4. Adjuvant Dabrafenib plus Trametinib in Stage IIIBRAF-Mutated Melanoma

5. Adjuvant nivolumab versus ipilimumab in resected stage IIIB–C and stage IV melanoma (CheckMate 238): 4-year results from a multicentre, double-blind, randomised, controlled, phase 3 trial

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