Adjuvant Nivolumab versus Ipilimumab in Resected Stage III/IV Melanoma: 5-Year Efficacy and Biomarker Results from CheckMate 238

Author:

Larkin James1ORCID,Del Vecchio Michele2ORCID,Mandalá Mario3ORCID,Gogas Helen4ORCID,Arance Fernandez Ana M.5ORCID,Dalle Stéphane6ORCID,Cowey Charles Lance7ORCID,Schenker Michael8ORCID,Grob Jean-Jacques9ORCID,Chiarion-Sileni Vanna10ORCID,Marquez-Rodas Ivan11ORCID,Butler Marcus O.12ORCID,Di Giacomo Anna Maria13ORCID,Middleton Mark R.14ORCID,Lutzky Jose15ORCID,de la Cruz-Merino Luis16ORCID,Arenberger Petr17ORCID,Atkinson Victoria18ORCID,Hill Andrew G.19ORCID,Fecher Leslie A.20ORCID,Millward Michael21ORCID,Nathan Paul D.22ORCID,Khushalani Nikhil I.23ORCID,Queirolo Paola24ORCID,Ritchings Corey25ORCID,Lobo Maurice25ORCID,Askelson Margarita25ORCID,Tang Hao25ORCID,Dolfi Sonia25ORCID,Ascierto Paolo A.26ORCID,Weber Jeffrey27ORCID

Affiliation:

1. 1The Royal Marsden NHS Foundation Trust, London, United Kingdom.

2. 2Fondazione IRCCS Istituto Nazionale dei Tumori, Milan, Italy.

3. 3Papa Giovanni XIII Hospital, Bergamo, Italy.

4. 4National and Kapodistrian University of Athens, Athens, Greece.

5. 5Hospital Clínic de Barcelona, Barcelona, Spain.

6. 6Hospices Civils de Lyon, Pierre Bénite, France.

7. 7Texas Oncology-Baylor Charles A. Sammons Cancer Center, Dallas, Texas.

8. 8Oncology Center Sf Nectarie Ltd., Craiova, Romania.

9. 9Aix Marseille University, Hôpital de la Timone, Marseille, France.

10. 10Veneto Institute of Oncology IOV – IRCCS, Padua, Italy.

11. 11General University Hospital Gregorio Marañón and CIBERONC, Madrid, Spain.

12. 12Princess Margaret Cancer Centre, Toronto, Ontario, Canada.

13. 13Center for Immuno-Oncology, University Hospital of Siena, Siena, Italy.

14. 14Churchill Hospital, Oxford, United Kingdom.

15. 15Sylvester Comprehensive Cancer Center, Miami, Florida.

16. 16Hospital Universitario Virgen Macarena, Clinical Oncology Department, University of Seville, Seville, Spain.

17. 17Charles University Third Faculty of Medicine and University Hospital Kralovske Vinohrady, Prague, Czech Republic.

18. 18Gallipoli Medical Research Foundation, Greenslopes Private Hospital, Greenslopes, Queensland, Australia.

19. 19Tasman Health Care, Southport, QLD, Australia.

20. 20University of Michigan Rogel Cancer Center, Ann Arbor, Michigan.

21. 21University of Western Australia and Sir Charles Gairdner Hospital, Nedlands, Western Australia, Australia.

22. 22Mount Vernon Hospital, Middlesex, United Kingdom.

23. 23H. Lee Moffitt Cancer Center, Tampa, Florida.

24. 24IEO, European Institute of Oncology IRCCS, Milan, Italy.

25. 25Bristol Myers Squibb, Princeton, New Jersey.

26. 26Istituto Nazionale Tumori IRCCS “Fondazione G. Pascale”, Naples, Italy.

27. 27Laura and Isaac Perlmutter Cancer Center at NYU Langone Health, New York.

Abstract

Abstract Purpose: In the phase III CheckMate 238 study, adjuvant nivolumab significantly improved recurrence-free survival (RFS) and distant metastasis-free survival versus ipilimumab in patients with resected stage IIIB–C or stage IV melanoma, with benefit sustained at 4 years. We report updated 5-year efficacy and biomarker findings. Patients and Methods: Patients with resected stage IIIB–C/IV melanoma were stratified by stage and baseline programmed death cell ligand 1 (PD-L1) expression and received nivolumab 3 mg/kg every 2 weeks or ipilimumab 10 mg/kg every 3 weeks for four doses and then every 12 weeks, both intravenously for 1 year until disease recurrence, unacceptable toxicity, or withdrawal of consent. The primary endpoint was RFS. Results: At a minimum follow-up of 62 months, RFS with nivolumab remained superior to ipilimumab (HR = 0.72; 95% confidence interval, 0.60–0.86; 5-year rates of 50% vs. 39%). Five-year distant metastasis-free survival (DMFS) rates were 58% with nivolumab versus 51% with ipilimumab. Five-year overall survival (OS) rates were 76% with nivolumab and 72% with ipilimumab (75% data maturity: 228 of 302 planned events). Higher levels of tumor mutational burden (TMB), tumor PD-L1, intratumoral CD8+ T cells and IFNγ-associated gene expression signature, and lower levels of peripheral serum C-reactive protein were associated with improved RFS and OS with both nivolumab and ipilimumab, albeit with limited clinically meaningful predictive value. Conclusions: Nivolumab is a proven adjuvant treatment for resected melanoma at high risk of recurrence, with sustained, long-term improvement in RFS and DMFS compared with ipilimumab and high OS rates. Identification of additional biomarkers is needed to better predict treatment outcome. See related commentary by Augustin and Luke, p. 3253

Funder

Bristol-Myers Squibb

Ono Pharmaceutical

Publisher

American Association for Cancer Research (AACR)

Subject

Cancer Research,Oncology

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