title: Randomised, double-blind trial of carboplatin and paclitaxel with daily oral cediranib or placebo in patients with advanced non-small cell lung cancer: NCIC Clinical Trials Group study BR29.
abstract: BACKGROUND
  This randomised double-blind placebo-controlled study evaluated the addition of cediranib, an inhibitor of vascular endothelial growth factor receptors 1-3, to standard carboplatin/paclitaxel chemotherapy in advanced non-small cell lung cancer.
  
  
  METHODS
  Eligible patients received paclitaxel (200mg/m(2)) and carboplatin (area under the concentration time curve 6) intravenously every 3 weeks. Daily oral cediranib/placebo 20mg was commenced day 1 of cycle 1 and continued as monotherapy after completion of 4-6 cycles of chemotherapy. The primary end-point of the study was overall survival (OS). The trial would continue to full accrual if an interim analysis (IA) for progression-free survival (PFS), performed after 170 events of progression or death in the first 260 randomised patients, revealed a hazard ratio (HR) for PFS of ⩽ 0.70.
  
  
  RESULTS
  The trial was halted for futility at the IA (HR for PFS 0.89, 95% confidence interval [CI] 0.66-1.20, p = 0.45). A final analysis was performed on all 306 enrolled patients. The addition of cediranib increased response rate ([RR] 52% versus 34%, p = 0.001) but did not significantly improve PFS (HR 0.91, 95% CI 0.71-1.18, p = 0.49) or OS (HR 0.94, 95% CI 0.69-1.30, p=0.72). Cediranib patients had more grade 3 hypertension, diarrhoea and anorexia.
  
  
  CONCLUSIONS
  The addition of cediranib 20mg daily to carboplatin/paclitaxel chemotherapy increased RR and toxicity, but not survival.
authors.affiliation: The NCIC Clinical Trials Group, Kingston, Ontario, Canada; The Australasian Lung Cancer Trials Group and the NHMRC Clinical Trials Centre, University of Sydney, New South Wales, Australia. Electronic address: slaurie@toh.on.ca.
authors.forename: S A
authors.initials: SA
authors.lastname: Laurie
authors.affiliation: The NCIC Clinical Trials Group, Kingston, Ontario, Canada; The Australasian Lung Cancer Trials Group and the NHMRC Clinical Trials Centre, University of Sydney, New South Wales, Australia.
authors.forename: B J
authors.initials: BJ
authors.lastname: Solomon
authors.affiliation: The NCIC Clinical Trials Group, Kingston, Ontario, Canada; The Australasian Lung Cancer Trials Group and the NHMRC Clinical Trials Centre, University of Sydney, New South Wales, Australia.
authors.forename: L
authors.initials: L
authors.lastname: Seymour
authors.affiliation: The NCIC Clinical Trials Group, Kingston, Ontario, Canada; The Australasian Lung Cancer Trials Group and the NHMRC Clinical Trials Centre, University of Sydney, New South Wales, Australia.
authors.forename: P M
authors.initials: PM
authors.lastname: Ellis
authors.affiliation: The NCIC Clinical Trials Group, Kingston, Ontario, Canada; The Australasian Lung Cancer Trials Group and the NHMRC Clinical Trials Centre, University of Sydney, New South Wales, Australia.
authors.forename: G D
authors.initials: GD
authors.lastname: Goss
authors.affiliation: The NCIC Clinical Trials Group, Kingston, Ontario, Canada; The Australasian Lung Cancer Trials Group and the NHMRC Clinical Trials Centre, University of Sydney, New South Wales, Australia.
authors.forename: F A
authors.initials: FA
authors.lastname: Shepherd
authors.affiliation: The NCIC Clinical Trials Group, Kingston, Ontario, Canada; The Australasian Lung Cancer Trials Group and the NHMRC Clinical Trials Centre, University of Sydney, New South Wales, Australia.
authors.forename: M J
authors.initials: MJ
authors.lastname: Boyer
authors.affiliation: The NCIC Clinical Trials Group, Kingston, Ontario, Canada; The Australasian Lung Cancer Trials Group and the NHMRC Clinical Trials Centre, University of Sydney, New South Wales, Australia.
authors.forename: A M
authors.initials: AM
authors.lastname: Arnold
authors.affiliation: The NCIC Clinical Trials Group, Kingston, Ontario, Canada; The Australasian Lung Cancer Trials Group and the NHMRC Clinical Trials Centre, University of Sydney, New South Wales, Australia.
authors.forename: P
authors.initials: P
authors.lastname: Clingan
authors.affiliation: The NCIC Clinical Trials Group, Kingston, Ontario, Canada; The Australasian Lung Cancer Trials Group and the NHMRC Clinical Trials Centre, University of Sydney, New South Wales, Australia.
authors.forename: F
authors.initials: F
authors.lastname: Laberge
authors.affiliation: The NCIC Clinical Trials Group, Kingston, Ontario, Canada; The Australasian Lung Cancer Trials Group and the NHMRC Clinical Trials Centre, University of Sydney, New South Wales, Australia.
authors.forename: D
authors.initials: D
authors.lastname: Fenton
authors.affiliation: The NCIC Clinical Trials Group, Kingston, Ontario, Canada; The Australasian Lung Cancer Trials Group and the NHMRC Clinical Trials Centre, University of Sydney, New South Wales, Australia.
authors.forename: V
authors.initials: V
authors.lastname: Hirsh
authors.affiliation: The NCIC Clinical Trials Group, Kingston, Ontario, Canada; The Australasian Lung Cancer Trials Group and the NHMRC Clinical Trials Centre, University of Sydney, New South Wales, Australia.
authors.forename: M
authors.initials: M
authors.lastname: Zukin
authors.affiliation: The NCIC Clinical Trials Group, Kingston, Ontario, Canada; The Australasian Lung Cancer Trials Group and the NHMRC Clinical Trials Centre, University of Sydney, New South Wales, Australia.
authors.forename: M R
authors.initials: MR
authors.lastname: Stockler
authors.affiliation: The NCIC Clinical Trials Group, Kingston, Ontario, Canada; The Australasian Lung Cancer Trials Group and the NHMRC Clinical Trials Centre, University of Sydney, New South Wales, Australia.
authors.forename: C W
authors.initials: CW
authors.lastname: Lee
authors.affiliation: The NCIC Clinical Trials Group, Kingston, Ontario, Canada; The Australasian Lung Cancer Trials Group and the NHMRC Clinical Trials Centre, University of Sydney, New South Wales, Australia.
authors.forename: E X
authors.initials: EX
authors.lastname: Chen
authors.affiliation: The NCIC Clinical Trials Group, Kingston, Ontario, Canada; The Australasian Lung Cancer Trials Group and the NHMRC Clinical Trials Centre, University of Sydney, New South Wales, Australia.
authors.forename: A
authors.initials: A
authors.lastname: Montenegro
authors.affiliation: The NCIC Clinical Trials Group, Kingston, Ontario, Canada; The Australasian Lung Cancer Trials Group and the NHMRC Clinical Trials Centre, University of Sydney, New South Wales, Australia.
authors.forename: K
authors.initials: K
authors.lastname: Ding
authors.affiliation: The NCIC Clinical Trials Group, Kingston, Ontario, Canada; The Australasian Lung Cancer Trials Group and the NHMRC Clinical Trials Centre, University of Sydney, New South Wales, Australia.
authors.forename: P A
authors.initials: PA
authors.lastname: Bradbury
mesh_terms: D000284:Administration, Oral; D000328:Adult; D000368:Aged; D000369:Aged, 80 and over; D000971:Antineoplastic Combined Chemotherapy Protocols / Q000008:administration & dosage*; D016190:Carboplatin / Q000008:administration & dosage*; D002289:Carcinoma, Non-Small-Cell Lung / Q000188:drug therapy* / Q000401:mortality / Q000473:pathology; D018450:Disease Progression; D004311:Double-Blind Method; D004334:Drug Administration Schedule; D005260:Female; D006801:Humans; D008175:Lung Neoplasms / Q000188:drug therapy* / Q000401:mortality / Q000473:pathology; D008297:Male; D008875:Middle Aged; D017239:Paclitaxel / Q000008:administration & dosage*; D010919:Placebos; D011799:Quinazolines / Q000008:administration & dosage*; D016019:Survival Analysis; D055815:Young Adult; D007211:Indoles
chemical_list: D016190:Carboplatin; D017239:Paclitaxel; D010919:Placebos; D011799:Quinazolines; C500926:cediranib; D007211:Indoles
keywords: Angiogenesis inhibitor; Non-small cell; Phase III; Systemic therapy