Статья

Improved Survival with Ipilimumab in Patients with Metastatic Melanoma

F. Stephen HodiDana-Farber Cancer Institute, Boston, MA 02115, USA. [email protected]Steven O’DayAngeles Clinic and Research Institute, Los AngelesDavid F. McDermottBeth Israel Deaconess Medical CenterRobert WeberJeffrey A. SosmanVanderbilt University Medical Center, NashvilleJohn B.A.G. HaanenNetherlands Cancer InstituteRené GonzálezUniversity of Colorado Cancer Center, AuroraCaroline RobertInstitut Gustave Roussy, Villejuif, FranceDirk SchadendorfUniversity Hospital Essen, EssenJessica C. HasselGerman Cancer Research Center, University of Mannheim, MannheimWallace AkerleyHuntsman Cancer Institute, Salt Lake CityAlfons J.M. van den EertweghVU University Medical CenterJose LutzkyMount Sinai Comprehensive Cancer Center, MiamiPaul LoriganChristie Hospital NHS Trust, ManchesterJulia VaübelUniversity Hospital Essen, EssenGerald P. LinetteWashington University School of Medicine, St. LouisDavid HoggPrincess Margaret Hospital, TorontoChristian H. OttensmeierSouthampton University Hospitals, SouthamptonCélèste LebbéSaint Louis Hospital, ParisChristian PeschelIan QuirtPrincess Margaret Hospital, TorontoJoseph I. ClarkLoyola University Medical Center, Maywood, ILJedd D. WolchokMemorial Sloan-Kettering Cancer Center, New YorkJeffrey S. WeberH. Lee Moffitt Cancer Center, Tampa, FLJason TianMichael YellinGeoffrey NicholAxel HoosBristol-Myers Squibb, Wallingford, CTWalter J. UrbaEarle A. Chiles Research Institute, Portland, OR

2010en

ABI

Аннотация

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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Идентификаторы

DOI: 10.1056/nejmoa1003466

Цитирования и источники

Цитирований: 9Использованных источников: 0

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