Nivolumab for Resected Stage III or IV Melanoma at 9 Years
Paolo A. Ascierto, Michele Del Vecchio, Barbara Merelli, Helen Gogas, Ana Arance, Stéphane Dalle, Charles Lance Cowey, Michael Schenker, Caroline Gaudy‐Marqueste, Jacopo Pigozzo, Iván Márquez‐Rodas, Marcus O. Butler, Anna Maria Di Giacomo, Oleg Gligich, Luis de la Cruz‐Merino, Petr Arenberger, Victoria Atkinson, Paul C. Nathan, Andrew F. Hill, Michael Millward, Leslie A. Fecher, Nikhil I. Khushalani, Paola Queirolo, Raheela Soomro, Dhanrajsinh Rathod, Margarita Askelson, Melanie Pe Benito, Devanand Joseph, James Larkin
Abstract
BACKGROUND: In the CheckMate 238 trial, patients with resected stage IIIB-C or stage IV melanoma who were treated with nivolumab had longer recurrence-free survival than those who received ipilimumab. Data were needed on longer-term survival. METHODS: We randomly assigned patients in a 1:1 ratio to receive an intravenous infusion of nivolumab (at a dose of 3 mg per kilogram of body weight every 2 weeks) or ipilimumab (at a dose of 10 mg per kilogram every 3 weeks for four doses, then every 12 weeks) for up to 1 year or until disease recurrence or the occurrence of unacceptable toxic effects. Randomization was stratified according to disease stage and status with respect to programmed cell death ligand 1. The primary end point was recurrence-free survival; secondary end points included overall and distant metastasis-free survival and safety. RESULTS: At a minimum follow-up of nearly 9 years (107 months), the median duration of recurrence-free survival was 61.1 months with nivolumab and 24.2 months with ipilimumab (hazard ratio for recurrence or death, 0.76; 95% confidence interval [CI], 0.63 to 0.90); 9-year recurrence-free survival was 44% and 37%, respectively. The median duration of distant metastasis-free survival in patients with stage III melanoma was more than 9 years with nivolumab and 83.8 months with ipilimumab, with 9-year survival of 54% and 48%, respectively (hazard ratio for distant metastasis or death, 0.81; 95% CI, 0.65 to 1.00). The median overall survival was more than 9 years in both trial groups, with 9-year survival of 69% in the nivolumab group and 65% in the ipilimumab group (hazard ratio for death, 0.88; 95.03% CI, 0.69 to 1.11). The rates of death from melanoma at 9 years were 26% with nivolumab and 30% with ipilimumab (hazard ratio, 0.87; 95% CI, 0.67 to 1.13). Subsequent systemic therapy was administered to fewer patients in the nivolumab group than in the ipilimumab group (37.3% vs. 44.6%). No new late adverse events were reported. CONCLUSIONS: The 9-year final data support a sustained finding of longer recurrence-free survival with nivolumab than with ipilimumab. (Funded by Bristol Myers Squibb and Ono Pharmaceutical; CheckMate 238 ClinicalTrials.gov number, NCT02388906; Eudra-CT number, 2014-002351-26.).