title: Ipilimumab in combination with paclitaxel and carboplatin as first-line therapy in extensive-disease-small-cell lung cancer: results from a randomized, double-blind, multicenter phase 2 trial.
abstract: BACKGROUND
  Ipilimumab, an anti-CTLA4 monoclonal antibody, demonstrated survival benefit in melanoma with immune-related (ir) adverse events (irAEs) managed by the protocol-defined guidelines. This phase 2 study evaluated ipilimumab+paclitaxel (Taxol)/carboplatin in extensive-disease-small-cell lung cancer (ED-SCLC).
  
  
  METHODS
  Patients (n=130) with chemotherapy-naïve ED-SCLC were randomized 1: 1: 1 to receive paclitaxel (175 mg/m2)/carboplatin (area under the curve=6) with either placebo (control) or ipilimumab 10 mg/kg in two alternative regimens, concurrent ipilimumab (ipilimumab+paclitaxel/carboplatin followed by placebo+paclitaxel/carboplatin) or phased ipilimumab (placebo+paclitaxel/carboplatin followed by ipilimumab+paclitaxel/carboplatin). Treatment was administered every 3 weeks for a maximum of 18 weeks (induction), followed by maintenance ipilimumab or placebo every 12 weeks. End points included progression-free survival (PFS), irPFS, best overall response rate (BORR); irBORR, overall survival (OS), and safety.
  
  
  RESULTS
  Phased ipilimumab, but not concurrent ipilimumab, improved irPFS versus control [HR (hazard ratio)=0.64; P=0.03]. No improvement in PFS (HR=0.93; P=0.37) or OS (HR=0.75; P=0.13) occurred. Phased ipilimumab, concurrent ipilimumab and control, respectively, were associated with median irPFS of 6.4, 5.7 and 5.3 months; median PFS of 5.2, 3.9 and 5.2 months; median OS of 12.9, 9.1 and 9.9 months. Overall rates of grade 3/4 irAEs were 17, 21 and 9% for phased ipilimumab, concurrent ipilimumab and control, respectively.
  
  
  CONCLUSIONS
  These results suggest further investigation of ipilimumab in ED-SCLC.
authors.affiliation: Department of Thoracic Oncology, Hospital Grosshansdorf, Grosshansdorf, Germany. dr.martin.reck@web.de
authors.forename: M
authors.initials: M
authors.lastname: Reck
authors.forename: I
authors.initials: I
authors.lastname: Bondarenko
authors.forename: A
authors.initials: A
authors.lastname: Luft
authors.forename: P
authors.initials: P
authors.lastname: Serwatowski
authors.forename: F
authors.initials: F
authors.lastname: Barlesi
authors.forename: R
authors.initials: R
authors.lastname: Chacko
authors.forename: M
authors.initials: M
authors.lastname: Sebastian
authors.forename: H
authors.initials: H
authors.lastname: Lu
authors.forename: J-M
authors.initials: JM
authors.lastname: Cuillerot
authors.forename: T J
authors.initials: TJ
authors.lastname: Lynch
mesh_terms: D000911:Antibodies, Monoclonal / Q000008:administration & dosage; D000971:Antineoplastic Combined Chemotherapy Protocols / Q000009:adverse effects / Q000627:therapeutic use*; D016190:Carboplatin / Q000008:administration & dosage; D004311:Double-Blind Method; D006801:Humans; D000074324:Ipilimumab; D008175:Lung Neoplasms / Q000188:drug therapy*; D017239:Paclitaxel / Q000008:administration & dosage; D010919:Placebos
chemical_list: D000911:Antibodies, Monoclonal; D000074324:Ipilimumab; D010919:Placebos; D016190:Carboplatin; D017239:Paclitaxel