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

IntroductionThis 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. MethodsEligible patients received paclitaxel (200mg/m2) and carboplatin (area under the concentration time curve 6) intravenously every 3weeks. 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. ResultsThe 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. ConclusionsThe addition of cediranib 20mg daily to carboplatin/paclitaxel chemotherapy increased RR and toxicity, but not survival.