title: Randomized phase III trial of paclitaxel/carboplatin with or without PF-3512676 (Toll-like receptor 9 agonist) as first-line treatment for advanced non-small-cell lung cancer.
abstract: OBJECTIVE
  This phase III study examined efficacy of the synthetic Toll-like receptor 9-activating oligodeoxynucleotide PF-3512676 in combination with standard paclitaxel/carboplatin chemotherapy in patients with advanced non-small-cell lung cancer (NSCLC).
  
  
  METHODS
  Chemotherapy-naive patients with stage IIIB or IV NSCLC were randomly assigned (1:1) to receive up to six courses of paclitaxel/carboplatin (intravenous paclitaxel 200 mg/m(2) and carboplatin at area under the [concentration-time] curve 6 on day 1 of a 3-week cycle) alone (control arm) or in combination with 0.2 mg/kg subcutaneous PF-3512676 on days 8 and 15 (investigational arm). Primary end point was overall survival (OS).
  
  
  RESULTS
  Baseline demographics were similar across arms (N = 828). Most patients (88%) had stage IV disease. Median OS and median progression-free survival (PFS) were similar (OS: investigational arm, 10.0 months v control arm, 9.8 months; P = .56; PFS: investigational arm, 4.8 months v control arm, 4.7 months; P = .79). Most commonly reported PF-3512676-related adverse events (AEs) were mild-to-moderate local injection site reactions, pyrexia, and flu-like symptoms. In the investigational arm, grades 3 to 4 AEs, including neutropenia, thrombocytopenia, and anemia, were more frequent, and more patients had one or more sepsis-related AEs versus controls (17 v 3). At first interim analysis, the Data Safety Monitoring Committee recommended study discontinuation because of lack of incremental efficacy and more sepsis-related serious AEs in the PF-3512676 arm. Administration of PF-3512676, but not chemotherapy, was halted.
  
  
  CONCLUSIONS
  Addition of PF-3512676 to paclitaxel/carboplatin did not improve OS or PFS versus paclitaxel/carboplatin alone for first-line treatment of patients with advanced NSCLC but did increase toxicity. This regimen cannot be recommended for treating patients with advanced NSCLC.
authors.affiliation: McGill University Health Center, Royal Victoria Hospital, Montreal, QC, Canada. vera.hirsh@muhc.mcgill.ca
authors.forename: Vera
authors.initials: V
authors.lastname: Hirsh
authors.forename: Luis
authors.initials: L
authors.lastname: Paz-Ares
authors.forename: Michael
authors.initials: M
authors.lastname: Boyer
authors.forename: Rafael
authors.initials: R
authors.lastname: Rosell
authors.forename: Gary
authors.initials: G
authors.lastname: Middleton
authors.forename: Wilfried E E
authors.initials: WE
authors.lastname: Eberhardt
authors.forename: Aleksandra
authors.initials: A
authors.lastname: Szczesna
authors.forename: Pavel
authors.initials: P
authors.lastname: Reiterer
authors.forename: Mansoor
authors.initials: M
authors.lastname: Saleh
authors.forename: Oscar
authors.initials: O
authors.lastname: Arrieta
authors.forename: Emilio
authors.initials: E
authors.lastname: Bajetta
authors.forename: Roy T
authors.initials: RT
authors.lastname: Webb
authors.forename: Johannes
authors.initials: J
authors.lastname: Raats
authors.forename: Rebecca J
authors.initials: RJ
authors.lastname: Benner
authors.forename: Camilla
authors.initials: C
authors.lastname: Fowst
authors.forename: Sandra J
authors.initials: SJ
authors.lastname: Meech
authors.forename: David
authors.initials: D
authors.lastname: Readett
authors.forename: Joan H
authors.initials: JH
authors.lastname: Schiller
mesh_terms: D000328:Adult; D000368:Aged; D000369:Aged, 80 and over; D000971:Antineoplastic Combined Chemotherapy Protocols / Q000627:therapeutic use*; D016190:Carboplatin / Q000008:administration & dosage*; D002289:Carcinoma, Non-Small-Cell Lung / Q000188:drug therapy*; D018450:Disease Progression; D005260:Female; D006801:Humans; D008175:Lung Neoplasms / Q000188:drug therapy*; D008297:Male; D008875:Middle Aged; D009838:Oligodeoxyribonucleotides / Q000008:administration & dosage*; D017239:Paclitaxel / Q000008:administration & dosage*; D051217:Toll-Like Receptor 9 / Q000819:agonists*; D016896:Treatment Outcome
chemical_list: D009838:Oligodeoxyribonucleotides; C483020:ProMune; D051217:Toll-Like Receptor 9; D016190:Carboplatin; D017239:Paclitaxel