From the Dana-Farber Cancer Institute (F.S.H.) and Beth Israel Deaconess Medical Center (D.F.M.) - both in Boston; the Angeles Clinic and Research Institute, Los Angeles (S.J.O.); St. Mary's Medical Center, San Francisco (R.W.W.); Vanderbilt University Medical Center, Nashville (J.A.S.); Netherlands Cancer Institute (J.B.H.) and VU University Medical Center (A.J.M.E.) - both in Amsterdam; University of Colorado Cancer Center, Aurora (R.G.); Institut Gustave Roussy, Villejuif, France (C.R.); University Hospital Essen, Essen (D.S., J.M.V.), German Cancer Research Center, University of Mannheim, Mannheim (J.C.H.), and Technical University Munich, Munich (C.P.) - all in Germany; Huntsman Cancer Institute, Salt Lake City (W.A.); Mount Sinai Comprehensive Cancer Center, Miami (J.L.); Christie Hospital NHS Trust, Manchester (P.L.), and Southampton University Hospitals, Southampton (C.H.O.) - both in the United Kingdom; Washington University School of Medicine, St. Louis (G.P.L.); Princess Margaret Hospital, Toronto (D.H., I.Q.); Saint Louis Hospital, Paris (C.L.); Loyola University Medical Center, Maywood, IL (J.I.C.); Memorial Sloan-Kettering Cancer Center, New York (J.D.W.); H. Lee Moffitt Cancer Center, Tampa, FL (J.S.W.); Medarex, Bloomsbury, NJ (J.T., M.J.Y., G.M.N.); Bristol-Myers Squibb, Wallingford, CT (A.H.); and the Earle A. Chiles Research Institute, Portland, OR (W.J.U.). Drs. Hodi and O'Day contributed equally to this article.Participating investigators are listed in the Appendix.This article (10.1056/NEJMoa1003466) was published on June 5, 2010, at NEJM.org.
N Engl J Med. 2010 Jun 5.
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.
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.
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.
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. (ClinicalTrials.gov number, NCT00094653.) Copyright 2010 Massachusetts Medical Society.
PMID: 20525992 [PubMed - as supplied by publisher] Source: National Library of Medicine.
