title: A phase II multicenter study of ipilimumab with or without dacarbazine in chemotherapy-naïve patients with advanced melanoma.
abstract: OBJECTIVE
  Ipilimumab is a fully human, anti-cytotoxic T-lymphocyte antigen-4 (CTLA-4) monoclonal antibody that has demonstrated antitumor activity in advanced melanoma. We evaluated the safety and efficacy of ipilimumab alone and in combination with dacarbazine (DTIC) in patients with unresectable, metastatic melanoma.
  
  
  METHODS
  Chemotherapy-naïve patients were randomized in this multicenter, phase II study to receive ipilimumab at 3 mg/kg every 4 weeks for four doses either alone or with up to six 5-day courses of DTIC at 250 mg/m(2)/day. The primary efficacy endpoint was objective response rate.
  
  
  RESULTS
  Seventy-two patients were treated per-protocol (ipilimumab plus DTIC, n = 35; ipilimumab, n = 37). The objective response rate was 14.3% (95% CI, 4.8-30.3) with ipilimumab plus DTIC and was 5.4% (95% CI, 0.7-18.2) with ipilimumab alone. At a median follow-up of 20.9 and 16.4 months for ipilimumab plus DTIC (n = 32) and ipilimumab alone (n = 32), respectively, median overall survival was 14.3 months (95% CI, 10.2-18.8) and 11.4 months (95% CI, 6.1-15.6); 12-month, 24-month, and 36-month survival rates were 62%, 24% and 20% for the ipilimumab plus DTIC group and were 45%, 21% and 9% for the ipilimumab alone group, respectively. Immune-related adverse events were, in general, medically manageable and occurred in 65.7% of patients in the combination group versus 53.8% in the monotherapy group, with 17.1% and 7.7% ≥grade 3, respectively.
  
  
  CONCLUSIONS
  Ipilimumab therapy resulted in clinically meaningful responses in advanced melanoma patients, and the results support further investigations of ipilimumab in combination with DTIC.
authors.affiliation: Arizona Cancer Center, University of Arizona, 1515 North Campbell Avenue, Tucson, AZ 85724, USA. ehersh@azcc.arizona.edu
authors.forename: Evan M
authors.initials: EM
authors.lastname: Hersh
authors.forename: Steven J
authors.initials: SJ
authors.lastname: O'Day
authors.forename: John
authors.initials: J
authors.lastname: Powderly
authors.forename: Khuda D
authors.initials: KD
authors.lastname: Khan
authors.forename: Anna C
authors.initials: AC
authors.lastname: Pavlick
authors.forename: Lee D
authors.initials: LD
authors.lastname: Cranmer
authors.forename: Wolfram E
authors.initials: WE
authors.lastname: Samlowski
authors.forename: Geoffrey M
authors.initials: GM
authors.lastname: Nichol
authors.forename: Michael J
authors.initials: MJ
authors.lastname: Yellin
authors.forename: Jeffrey S
authors.initials: JS
authors.lastname: Weber
mesh_terms: D000328:Adult; D000368:Aged; D000369:Aged, 80 and over; D000911:Antibodies, Monoclonal / Q000009:adverse effects / Q000493:pharmacokinetics / Q000627:therapeutic use*; D000970:Antineoplastic Agents / Q000009:adverse effects / Q000493:pharmacokinetics / Q000627:therapeutic use*; D000971:Antineoplastic Combined Chemotherapy Protocols / Q000009:adverse effects / Q000493:pharmacokinetics / Q000627:therapeutic use*; D003606:Dacarbazine / Q000009:adverse effects / Q000493:pharmacokinetics / Q000627:therapeutic use*; D003710:Demography; D005260:Female; D006801:Humans; D000074324:Ipilimumab; D053208:Kaplan-Meier Estimate; D016131:Lymphocyte Subsets / Q000276:immunology; D008297:Male; D008545:Melanoma / Q000188:drug therapy* / Q000276:immunology / Q000473:pathology*; D008875:Middle Aged; D009367:Neoplasm Staging; D016896:Treatment Outcome
chemical_list: D000911:Antibodies, Monoclonal; D000970:Antineoplastic Agents; D000074324:Ipilimumab; D003606:Dacarbazine