Improved survival with ipilimumab in patients with metastatic melanoma
- PMID: 20525992
- PMCID: PMC3549297
- DOI: 10.1056/NEJMoa1003466
Improved survival with ipilimumab in patients with metastatic melanoma
Erratum in
- N Engl J Med. 2010 Sep 23;363(13):1290
Abstract
Background: An improvement in overall survival among patients with metastatic melanoma has been an elusive goal. In this phase 3 study, ipilimumab--which blocks cytotoxic T-lymphocyte-associated antigen 4 to potentiate an antitumor T-cell response--administered with or without a glycoprotein 100 (gp100) peptide vaccine was compared with gp100 alone in patients with previously treated metastatic melanoma.
Methods: A total of 676 HLA-A*0201-positive patients with unresectable stage III or IV melanoma, whose disease had progressed while they were receiving therapy for metastatic disease, were randomly assigned, in a 3:1:1 ratio, to receive ipilimumab plus gp100 (403 patients), ipilimumab alone (137), or gp100 alone (136). Ipilimumab, at a dose of 3 mg per kilogram of body weight, was administered with or without gp100 every 3 weeks for up to four treatments (induction). Eligible patients could receive reinduction therapy. The primary end point was overall survival.
Results: The median overall survival was 10.0 months among patients receiving ipilimumab plus gp100, as compared with 6.4 months among patients receiving gp100 alone (hazard ratio for death, 0.68; P<0.001). The median overall survival with ipilimumab alone was 10.1 months (hazard ratio for death in the comparison with gp100 alone, 0.66; P=0.003). No difference in overall survival was detected between the ipilimumab groups (hazard ratio with ipilimumab plus gp100, 1.04; P=0.76). Grade 3 or 4 immune-related adverse events occurred in 10 to 15% of patients treated with ipilimumab and in 3% treated with gp100 alone. There were 14 deaths related to the study drugs (2.1%), and 7 were associated with immune-related adverse events.
Conclusions: Ipilimumab, with or without a gp100 peptide vaccine, as compared with gp100 alone, improved overall survival in patients with previously treated metastatic melanoma. Adverse events can be severe, long-lasting, or both, but most are reversible with appropriate treatment. (Funded by Medarex and Bristol-Myers Squibb; ClinicalTrials.gov number, NCT00094653.)
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Comment in
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Treating cancer by targeting the immune system.N Engl J Med. 2010 Aug 19;363(8):779-81. doi: 10.1056/NEJMe1006416. N Engl J Med. 2010. PMID: 20818880 No abstract available.
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Ipilimumab: attenuation of an inhibitory immune checkpoint improves survival in metastatic melanoma.Expert Rev Anticancer Ther. 2010 Nov;10(11):1697-701. doi: 10.1586/era.10.144. Expert Rev Anticancer Ther. 2010. PMID: 21080797 Review.
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Diarrhea from ipilimumab in melanoma.N Engl J Med. 2010 Dec 2;363(23):2262; author reply 2262-3. doi: 10.1056/NEJMc1010475. N Engl J Med. 2010. PMID: 21121842 No abstract available.
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[Monoclonal antibody in the therapy of metastatic melanoma].Internist (Berl). 2011 Jul;52(7):902-3. doi: 10.1007/s00108-011-2885-5. Internist (Berl). 2011. PMID: 21656102 German. No abstract available.
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Use of ipilimumab in melanoma.Immunotherapy. 2011 Aug;3(8):927-30. doi: 10.2217/imt.11.77. Immunotherapy. 2011. PMID: 21843079 No abstract available.
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Treatment of advanced melanoma with immunological checkpoint block.Curr Oncol Rep. 2011 Dec;13(6):430-2. doi: 10.1007/s11912-011-0195-7. Curr Oncol Rep. 2011. PMID: 21938386 No abstract available.
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