Adjuvant Nivolumab versus Ipilimumab in Resected Stage III or IV Melanoma
- PMID: 28891423
- DOI: 10.1056/NEJMoa1709030
Adjuvant Nivolumab versus Ipilimumab in Resected Stage III or IV Melanoma
Abstract
Background: Nivolumab and ipilimumab are immune checkpoint inhibitors that have been approved for the treatment of advanced melanoma. In the United States, ipilimumab has also been approved as adjuvant therapy for melanoma on the basis of recurrence-free and overall survival rates that were higher than those with placebo in a phase 3 trial. We wanted to determine the efficacy of nivolumab versus ipilimumab for adjuvant therapy in patients with resected advanced melanoma.
Methods: In this randomized, double-blind, phase 3 trial, we randomly assigned 906 patients (≥15 years of age) who were undergoing complete resection of stage IIIB, IIIC, or IV melanoma to receive an intravenous infusion of either nivolumab at a dose of 3 mg per kilogram of body weight every 2 weeks (453 patients) or ipilimumab at a dose of 10 mg per kilogram every 3 weeks for four doses and then every 12 weeks (453 patients). The patients were treated for a period of up to 1 year or until disease recurrence, a report of unacceptable toxic effects, or withdrawal of consent. The primary end point was recurrence-free survival in the intention-to-treat population.
Results: At a minimum follow-up of 18 months, the 12-month rate of recurrence-free survival was 70.5% (95% confidence interval [CI], 66.1 to 74.5) in the nivolumab group and 60.8% (95% CI, 56.0 to 65.2) in the ipilimumab group (hazard ratio for disease recurrence or death, 0.65; 97.56% CI, 0.51 to 0.83; P<0.001). Treatment-related grade 3 or 4 adverse events were reported in 14.4% of the patients in the nivolumab group and in 45.9% of those in the ipilimumab group; treatment was discontinued because of any adverse event in 9.7% and 42.6% of the patients, respectively. Two deaths (0.4%) related to toxic effects were reported in the ipilimumab group more than 100 days after treatment.
Conclusions: Among patients undergoing resection of stage IIIB, IIIC, or IV melanoma, adjuvant therapy with nivolumab resulted in significantly longer recurrence-free survival and a lower rate of grade 3 or 4 adverse events than adjuvant therapy with ipilimumab. (Funded by Bristol-Myers Squibb and Ono Pharmaceutical; CheckMate 238 ClinicalTrials.gov number, NCT02388906 ; Eudra-CT number, 2014-002351-26 .).
Comment in
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Drug therapy: Moving on up - from stage IV into stage III.Nat Rev Clin Oncol. 2017 Nov;14(11):647. doi: 10.1038/nrclinonc.2017.159. Epub 2017 Sep 26. Nat Rev Clin Oncol. 2017. PMID: 28948976 No abstract available.
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Adjuvant Melanoma Therapy - Head-Spinning Progress.N Engl J Med. 2017 Nov 9;377(19):1888-1890. doi: 10.1056/NEJMe1711199. N Engl J Med. 2017. PMID: 29117487 No abstract available.
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Adjuvant Therapy in Resected Melanoma.N Engl J Med. 2018 Feb 15;378(7):678-9. doi: 10.1056/NEJMc1716071. N Engl J Med. 2018. PMID: 29446285 No abstract available.
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Adjuvant Therapy in Resected Melanoma.N Engl J Med. 2018 Feb 15;378(7):679. doi: 10.1056/NEJMc1716071. N Engl J Med. 2018. PMID: 29446287 No abstract available.
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A new era of proactive melanoma therapy: hit hard, hit early.Br J Dermatol. 2018 Apr;178(4):817-820. doi: 10.1111/bjd.16347. Br J Dermatol. 2018. PMID: 29668089 No abstract available.
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Estimation of Distant Metastasis-free Survival in Trials of Adjuvant Therapy for Melanoma.N Engl J Med. 2019 Apr 4;380(14):1374-1376. doi: 10.1056/NEJMc1902228. N Engl J Med. 2019. PMID: 30943345 No abstract available.
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