title: A phase III randomized study of gemcitabine and cisplatin with or without PF-3512676 (TLR9 agonist) as first-line treatment of advanced non-small-cell lung cancer.
abstract: BACKGROUND
  This open-label phase III study assessed the addition of Toll-like receptor 9-activating oligodeoxynucleotide PF-3512676 to gemcitabine/cisplatin chemotherapy in patients with non-small-cell lung cancer (NSCLC).
  
  
  METHODS
  Chemotherapy-naive patients with stage IIIB or IV NSCLC were randomized (1:1) to receive six or fewer 3-week cycles of i.v. gemcitabine (1250 mg/m2 on days 1 and 8) and cisplatin alone (75 mg/m2 on day 1, control arm) or combined with s.c. PF-3512676 0.2 mg/kg on days 8 and 15 of each chemotherapy cycle and weekly thereafter until progression or unacceptable toxicity (experimental arm). No crossover was planned. The primary end point was overall survival (OS).
  
  
  RESULTS
  A total of 839 patients were randomized. Baseline demographics were well balanced. Median OS (11.0 versus 10.7 months; P=0.98) and median progression-free survival (PFS) (both 5.1 months) were similar between groups. Grade≥3 hematologic adverse events (AEs), injection-site reactions, and influenza-like symptoms were more frequently reported among patients receiving PF-3512676. At the first-interim analysis, the Data Safety Monitoring Committee recommended study discontinuation. Administration of PF-3512676 was halted based on efficacy futility and increased grade≥3 AEs (experimental arm).
  
  
  CONCLUSIONS
  Addition of PF-3512676 to gemcitabine/cisplatin chemotherapy did not improve OS or PFS but did increase toxicity.
authors.affiliation: Interdisciplinary Thoracic Oncology, Department of Surgery, University Medical Center Mannheim, Heidelberg University, Mannheim, Germany. Electronic address: Prof.Manegold@t-online.de.
authors.forename: C
authors.initials: C
authors.lastname: Manegold
authors.affiliation: Bernie Banton Centre, University of Sydney, Sydney, Australia.
authors.forename: N
authors.initials: N
authors.lastname: van Zandwijk
authors.affiliation: 3rd Department, Regional Lung Diseases Hospital, Otwock, Poland.
authors.forename: A
authors.initials: A
authors.lastname: Szczesna
authors.affiliation: 3rd Faculty of Medicine, Charles University, Faculty Hospital Bulovka and Postgraduate Medical Institute, Prague, Czech Republic.
authors.forename: P
authors.initials: P
authors.lastname: Zatloukal
authors.affiliation: Department of Clinical Oncology, Queen Elizabeth Hospital, Kowloon, Hong Kong.
authors.forename: J S K
authors.initials: JSK
authors.lastname: Au
authors.affiliation: Department of Proliferative Diseases, Copernicus Memorial Hospital, Lodz.
authors.forename: M
authors.initials: M
authors.lastname: Blasinska-Morawiec
authors.affiliation: Chemotherapy Department, Specialistic Hospital Named After Professor A. Sokolowski, Szczecin-Zdunowo.
authors.forename: P
authors.initials: P
authors.lastname: Serwatowski
authors.affiliation: Lung and Thoracic Tumours Department, Maria Sklodowska-Curie Memorial Cancer Centre, Warsaw.
authors.forename: M
authors.initials: M
authors.lastname: Krzakowski
authors.affiliation: Department of Oncology and Radiology, Medical University of Gdansk, Gdansk, Poland.
authors.forename: J
authors.initials: J
authors.lastname: Jassem
authors.affiliation: Department of Medical Oncology, National Cancer Centre, Singapore.
authors.forename: E H
authors.initials: EH
authors.lastname: Tan
authors.affiliation: Pfizer Global Research and Development, New London, USA.
authors.forename: R J
authors.initials: RJ
authors.lastname: Benner
authors.affiliation: Pfizer Global Research and Development, Milan, Italy.
authors.forename: A
authors.initials: A
authors.lastname: Ingrosso
authors.affiliation: Pfizer Global Research and Development, New London, USA.
authors.forename: S J
authors.initials: SJ
authors.lastname: Meech
authors.affiliation: Pfizer Global Research and Development, New London, USA.
authors.forename: D
authors.initials: D
authors.lastname: Readett
authors.affiliation: Department of Medical Oncology, Christie Hospital, Manchester, UK.
authors.forename: N
authors.initials: N
authors.lastname: Thatcher
mesh_terms: D000328:Adult; D000368:Aged; D000369:Aged, 80 and over; D000971:Antineoplastic Combined Chemotherapy Protocols / Q000627:therapeutic use*; D002289:Carcinoma, Non-Small-Cell Lung / Q000188:drug therapy* / Q000401:mortality; D002945:Cisplatin / Q000008:administration & dosage / Q000009:adverse effects; D003841:Deoxycytidine / Q000008:administration & dosage / Q000009:adverse effects / Q000031:analogs & derivatives; D018572:Disease-Free Survival; D005260:Female; D006801:Humans; D053208:Kaplan-Meier Estimate; D008175:Lung Neoplasms / Q000188:drug therapy* / Q000401:mortality; D008297:Male; D008875:Middle Aged; D009367:Neoplasm Staging; D009838:Oligodeoxyribonucleotides / Q000008:administration & dosage* / Q000009:adverse effects; D016016:Proportional Hazards Models; D000093542:Gemcitabine
chemical_list: D009838:Oligodeoxyribonucleotides; C483020:ProMune; D003841:Deoxycytidine; D002945:Cisplatin; D000093542:Gemcitabine