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.
S A Laurie, B J Solomon, L Seymour, P M Ellis, G D Goss, F A Shepherd, M J Boyer, A M Arnold, P Clingan, F Laberge, D Fenton, V Hirsh, M Zukin, M R Stockler, C W Lee, E X Chen, A Montenegro, K Ding, P A Bradbury
Author Information
S A Laurie: 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.
B J Solomon: 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.
L Seymour: 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.
P M Ellis: 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.
G D Goss: 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.
F A Shepherd: 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.
M J Boyer: 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.
A M Arnold: 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.
P Clingan: 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.
F Laberge: 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.
D Fenton: 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.
V Hirsh: 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.
M Zukin: 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.
M R Stockler: 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.
C W Lee: 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.
E X Chen: 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.
A Montenegro: 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.
K Ding: 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.
P A Bradbury: 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.
INTRODUCTION: 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.
