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.

Aix Marseille University Hôpital de la Timone Marseille France

Bristol Myers Squibb Princeton New Jersey

Center for Immuno Oncology University Hospital of Siena Siena Italy

Charles University 3rd Faculty of Medicine and University Hospital Kralovske Vinohrady Prague Czech Republic

Churchill Hospital Oxford United Kingdom

Fondazione IRCCS Istituto Nazionale dei Tumori Milan Italy

Gallipoli Medical Research Foundation Greenslopes Private Hospital Greenslopes Queensland Australia

General University Hospital Gregorio Marañón and CIBERONC Madrid Spain

H Lee Moffitt Cancer Center Tampa Florida

Hospices Civils de Lyon Pierre Bénite France

Hospital Clínic de Barcelona Barcelona Spain

Hospital Universitario Virgen Macarena Clinical Oncology Department University of Seville Seville Spain

IEO European Institute of Oncology IRCCS Milan Italy

Istituto Nazionale Tumori IRCCS Fondazione G Pascale Naples Italy

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

Mount Vernon Hospital Middlesex United Kingdom

National and Kapodistrian University of Athens Athens Greece

Oncology Center Sf Nectarie Ltd Craiova Romania

Papa Giovanni XIII Hospital Bergamo Italy

Princess Margaret Cancer Centre Toronto Ontario Canada

Sylvester Comprehensive Cancer Center Miami Florida

Tasman Health Care Southport QLD Australia

Texas Oncology Baylor Charles A Sammons Cancer Center Dallas Texas

The Royal Marsden NHS Foundation Trust London United Kingdom

University of Michigan Rogel Cancer Center Ann Arbor Michigan

University of Western Australia and Sir Charles Gairdner Hospital Nedlands Western Australia Australia

Veneto Institute of Oncology IOV IRCCS Padua Italy

Clin Cancer Res. 2023 Sep 1;29(17):3253-3255. doi: 10.1158/1078-0432.CCR-23-1194. PubMed

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