Journal
CLINICAL CANCER RESEARCH
Volume 29, Issue 17, Pages 3352-3361Publisher
AMER ASSOC CANCER RESEARCH
DOI: 10.1158/1078-0432.CCR-22-3145
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The study demonstrates that adjuvant nivolumab significantly improves recurrence-free survival and distant metastasis-free survival in high-risk melanoma patients who have undergone surgical resection, with sustained long-term benefits. Biomarkers such as tumor mutational burden, tumor PD-L1, intratumoral CD8+ T cells and IFNy-associated gene expression signature are associated with improved treatment outcomes, but their predictive value is limited.
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 1/4 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 thorn T cells and IFNy-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.
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