From the Institute Gustave, Roussy, Villejuif (C.R.); Centre Hospitalier, Lyon Sud, Pierre Bénite (L.T.); Hôpital Saint Louis University, Paris (C.L.); and Hôpital de la Timone, Marseille (J.-J.G.) - all in France; Dnepropetrovsk State Medical Center, Dnepropetrovsk, Ukraine (I.B.); The Angeles Clinic and Research Institute, Santa Monica, CA (S.O.); H. Lee Moffitt Cancer Center and Research Institute, Tampa, FL (J.W.); University Medical Center, Tuebingen, Germany (C.G.); Cliniques Universitaires Saint-Luc, Brussels (J.-F.B.) and Bristol-Myers Squibb, Braine-l'Alleud (S.F.) - both in Belgium; Istituto Europeo di Oncologia, Milan (A.T.) and University Hospital of Siena, Siena (M.M.) - both in Italy; Mid Essex Hospitals National Health Service Trust, Essex, United Kingdom (N.D.); Oncology Specialists, Park Ridge, IL (J.R.); University of Kiel, Kiel, Germany (A.H.); Lady Davis Institute and Segal Cancer Center, Jewish General Hospital, McGill University, Montreal (W.M.); Hospital Clinic, Barcelona, Spain (P.G.); Hadassah Hebrew University Hospital, Sharett Institute of Oncology, Jerusalem, Israel (M.L.); Medical University of Vienna, Vienna (K.H.); Medimmune, Gaithersburg, MD (R.I.); Bristol-Myers Squibb, Wallingford, CT (T.-T.C., A.H.); Bristol-Myers Squibb, Lawrenceville, NJ (R.H.); and Memorial Sloan-Kettering Cancer Center, New York (J.D.W.).
N Engl J Med. 2011 Jun 5.
Ipilimumab monotherapy (at a dose of 3 mg per kilogram of body weight), as compared with glycoprotein 100, improved overall survival in a phase 3 study involving patients with previously treated metastatic melanoma. We conducted a phase 3 study of ipilimumab (10 mg per kilogram) plus dacarbazine in patients with previously untreated metastatic melanoma.
We randomly assigned 502 patients with previously untreated metastatic melanoma, in a 1:1 ratio, to ipilimumab (10 mg per kilogram) plus dacarbazine (850 mg per square meter of body-surface area) or dacarbazine (850 mg per square meter) plus placebo, given at weeks 1, 4, 7, and 10, followed by dacarbazine alone every 3 weeks through week 22. Patients with stable disease or an objective response and no dose-limiting toxic effects received ipilimumab or placebo every 12 weeks thereafter as maintenance therapy. The primary end point was overall survival.
Overall survival was significantly longer in the group receiving ipilimumab plus dacarbazine than in the group receiving dacarbazine plus placebo (11.2 months vs. 9.1 months, with higher survival rates in the ipilimumab-dacarbazine group at 1 year (47.3% vs. 36.3%), 2 years (28.5% vs. 17.9%), and 3 years (20.8% vs. 12.2%) (hazard ratio for death, 0.72; P<0.001). Grade 3 or 4 adverse events occurred in 56.3% of patients treated with ipilimumab plus dacarbazine, as compared with 27.5% treated with dacarbazine and placebo (P<0.001). No drug-related deaths or gastrointestinal perforations occurred in the ipilimumab-dacarbazine group.
Ipilimumab (at a dose of 10 mg per kilogram) in combination with dacarbazine, as compared with dacarbazine plus placebo, improved overall survival in patients with previously untreated metastatic melanoma. The types of adverse events were consistent with those seen in prior studies of ipilimumab; however, the rates of elevated liver-function values were higher and the rates of gastrointestinal events were lower than expected on the basis of prior studies. (Funded by Bristol-Myers Squibb; ClinicalTrials.gov number, NCT00324155 .).
PMID: 21639810 [PubMed - as supplied by publisher] Source: National Library of Medicine.
