Adjuvant Nivolumab Versus Ipilimumab in Resected Stage III/IV Melanoma: 5-Year Efficacy and Biomarker Results From CheckMate 238.
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Date
2023-04-14ICR Author
Author
Larkin, J
Del Vecchio, M
Mandala, M
Gogas, H
Arance, AM
Dalle, S
Cowey, CL
Schenker, M
Grob, J-J
Chiarion-Sileni, V
Marquez-Rodas, I
Butler, MO
Di Giacomo, AM
Middleton, MR
Lutzky, J
de la Cruz-Merino, L
Arenberger, P
Atkinson, V
Hill, AG
Fecher, LA
Millward, M
Nathan, PD
Khushalani, NI
Queirolo, P
Ritchings, C
Lobo, M
Askelson, M
Tang, H
Dolfi, S
Ascierto, PA
Weber, J
Type
Journal Article
Metadata
Show full item recordAbstract
PURPOSE: In the phase III CheckMate 238 study, adjuvant nivolumab (NIVO) significantly improved recurrence-free survival (RFS) and distant metastasis-free survival versus ipilimumab (IPI) 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 PD-L1 expression and received NIVO 3 mg/kg every 2 weeks or IPI 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 NIVO remained superior to IPI (HR 0.72; 95% CI, 0.60-0.86; 5-year rates of 50% versus 39%). 5-year DMFS rates were 58% with NIVO versus 51% with IPI. Five-year OS rates were 76% with NIVO and 72% with IPI (75% data maturity: 228 of 302 planned events). Higher levels of TMB, tumor PD-L1, intratumoral CD8+ T cells and interferon-gamma-associated gene expression signature, and lower levels of peripheral serum C-reactive protein were associated with improved RFS and OS with both NIVO and IPI, albeit with limited clinically meaningful predictive value. CONCLUSION: NIVO is a proven adjuvant treatment for resected melanoma at high-risk of recurrence, with sustained, long-term improvement in RFS and DMFS compared with IPI and high OS rates. Identification of additional biomarkers are needed to better predict treatment outcome.
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Language
eng
Date accepted
2023-04-12
License start date
2023-04-14
Citation
Clinical Cancer Research, 2023, pp. CCR-22-3145 -
Publisher
American Association for Cancer Research (AACR)