Prolonged Survival in Stage III Melanoma with Ipilimumab Adjuvant Therapy
- PMID: 27717298
- PMCID: PMC5648545
- DOI: 10.1056/NEJMoa1611299
Prolonged Survival in Stage III Melanoma with Ipilimumab Adjuvant Therapy
Erratum in
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Neoadjuvant PD-1 Blockade in Resectable Lung Cancer; Nivolumab and Ipilimumab in Advanced Melanoma; Overall Survival with Combined Nivolumab and Ipilimumab in Advanced Melanoma; Prolonged Survival in Stage III Melanoma with Ipilimumab Adjuvant Therapy; Combined Nivolumab and Ipilimumab or Monotherapy in Untreated Melanoma; Combined Nivolumab and Ipilimumab or Monotherapy in Untreated Melanoma; Nivolumab and Ipilimumab versus Ipilimumab in Untreated Melanoma; Rapid Eradication of a Bulky Melanoma Mass with One Dose of Immunotherapy; Genetic Basis for Clinical Response to CTLA-4 Blockade; Genetic Basis for Clinical Response to CTLA-4 Blockade in Melanoma; Nivolumab plus Ipilimumab in Advanced Melanoma; Safety and Tumor Responses with Lambrolizumab (Anti-PD-1) in Melanoma; Hepatotoxicity with Combination of Vemurafenib and Ipilimumab.N Engl J Med. 2018 Nov 29;379(22):2185. doi: 10.1056/NEJMx180040. Epub 2018 Nov 9. N Engl J Med. 2018. PMID: 31442371 No abstract available.
Abstract
Background: On the basis of data from a phase 2 trial that compared the checkpoint inhibitor ipilimumab at doses of 0.3 mg, 3 mg, and 10 mg per kilogram of body weight in patients with advanced melanoma, this phase 3 trial evaluated ipilimumab at a dose of 10 mg per kilogram in patients who had undergone complete resection of stage III melanoma.
Methods: After patients had undergone complete resection of stage III cutaneous melanoma, we randomly assigned them to receive ipilimumab at a dose of 10 mg per kilogram (475 patients) or placebo (476) every 3 weeks for four doses, then every 3 months for up to 3 years or until disease recurrence or an unacceptable level of toxic effects occurred. Recurrence-free survival was the primary end point. Secondary end points included overall survival, distant metastasis-free survival, and safety.
Results: At a median follow-up of 5.3 years, the 5-year rate of recurrence-free survival was 40.8% in the ipilimumab group, as compared with 30.3% in the placebo group (hazard ratio for recurrence or death, 0.76; 95% confidence interval [CI], 0.64 to 0.89; P<0.001). The rate of overall survival at 5 years was 65.4% in the ipilimumab group, as compared with 54.4% in the placebo group (hazard ratio for death, 0.72; 95.1% CI, 0.58 to 0.88; P=0.001). The rate of distant metastasis-free survival at 5 years was 48.3% in the ipilimumab group, as compared with 38.9% in the placebo group (hazard ratio for death or distant metastasis, 0.76; 95.8% CI, 0.64 to 0.92; P=0.002). Adverse events of grade 3 or 4 occurred in 54.1% of the patients in the ipilimumab group and in 26.2% of those in the placebo group. Immune-related adverse events of grade 3 or 4 occurred in 41.6% of the patients in the ipilimumab group and in 2.7% of those in the placebo group. In the ipilimumab group, 5 patients (1.1%) died owing to immune-related adverse events.
Conclusions: As adjuvant therapy for high-risk stage III melanoma, ipilimumab at a dose of 10 mg per kilogram resulted in significantly higher rates of recurrence-free survival, overall survival, and distant metastasis-free survival than placebo. There were more immune-related adverse events with ipilimumab than with placebo. (Funded by Bristol-Myers Squibb; ClinicalTrials.gov number, NCT00636168 , and EudraCT number, 2007-001974-10 .).
Conflict of interest statement
No other potential conflict of interest relevant to this article was reported.
Figures
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Comment in
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Ipilimumab Adjuvant Therapy in Melanoma.N Engl J Med. 2017 Jan 26;376(4):399. doi: 10.1056/NEJMc1615564. N Engl J Med. 2017. PMID: 28121506 No abstract available.
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Ipilimumab Adjuvant Therapy in Melanoma.N Engl J Med. 2017 Jan 26;376(4):398. doi: 10.1056/NEJMc1615564. N Engl J Med. 2017. PMID: 28125193 No abstract available.
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Ipilimumab Adjuvant Therapy in Melanoma.N Engl J Med. 2017 Jan 26;376(4):398-9. doi: 10.1056/NEJMc1615564. N Engl J Med. 2017. PMID: 28125194 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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