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

Autor:	Larkin J; The Royal Marsden NHS Foundation Trust, London, United Kingdom., Del Vecchio M; Fondazione IRCCS Istituto Nazionale dei Tumori, Milan, Italy., Mandalá M; Papa Giovanni XIII Hospital, Bergamo, Italy., Gogas H; National and Kapodistrian University of Athens, Athens, Greece., Arance Fernandez AM; Hospital Clínic de Barcelona, Barcelona, Spain., Dalle S; Hospices Civils de Lyon, Pierre Bénite, France., Cowey CL; Texas Oncology-Baylor Charles A. Sammons Cancer Center, Dallas, Texas., Schenker M; Oncology Center Sf Nectarie Ltd., Craiova, Romania., Grob JJ; Aix Marseille University, Hôpital de la Timone, Marseille, France., Chiarion-Sileni V; Veneto Institute of Oncology IOV - IRCCS, Padua, Italy., Marquez-Rodas I; General University Hospital Gregorio Marañón and CIBERONC, Madrid, Spain., Butler MO; Princess Margaret Cancer Centre, Toronto, Ontario, Canada., Di Giacomo AM; Center for Immuno-Oncology, University Hospital of Siena, Siena, Italy., Middleton MR; Churchill Hospital, Oxford, United Kingdom., Lutzky J; Sylvester Comprehensive Cancer Center, Miami, Florida., de la Cruz-Merino L; Hospital Universitario Virgen Macarena, Clinical Oncology Department, University of Seville, Seville, Spain., Arenberger P; Charles University Third Faculty of Medicine and University Hospital Kralovske Vinohrady, Prague, Czech Republic., Atkinson V; Gallipoli Medical Research Foundation, Greenslopes Private Hospital, Greenslopes, Queensland, Australia., Hill AG; Tasman Health Care, Southport, QLD, Australia., Fecher LA; University of Michigan Rogel Cancer Center, Ann Arbor, Michigan., Millward M; University of Western Australia and Sir Charles Gairdner Hospital, Nedlands, Western Australia, Australia., Nathan PD; Mount Vernon Hospital, Middlesex, United Kingdom., Khushalani NI; H. Lee Moffitt Cancer Center, Tampa, Florida., Queirolo P; IEO, European Institute of Oncology IRCCS, Milan, Italy., Ritchings C; Bristol Myers Squibb, Princeton, New Jersey., Lobo M; Bristol Myers Squibb, Princeton, New Jersey., Askelson M; Bristol Myers Squibb, Princeton, New Jersey., Tang H; Bristol Myers Squibb, Princeton, New Jersey., Dolfi S; Bristol Myers Squibb, Princeton, New Jersey., Ascierto PA; Istituto Nazionale Tumori IRCCS 'Fondazione G. Pascale', Naples, Italy., Weber J; Laura and Isaac Perlmutter Cancer Center at NYU Langone Health, New York.
Jazyk:	angličtina
Zdroj:	Clinical cancer research : an official journal of the American Association for Cancer Research [Clin Cancer Res] 2023 Sep 01; Vol. 29 (17), pp. 3352-3361.
DOI:	10.1158/1078-0432.CCR-22-3145
Abstrakt:	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. (©2023 The Authors; Published by the American Association for Cancer Research.)
Databáze:	MEDLINE
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