Cediranib monotherapy in patients with advanced renal cell carcinoma: Results of a randomised phase II study

Background: Cediranib is a highly potent vascular endothelial growth factor (VEGF) signalling inhibitor with activity against VEGF receptors 1, 2 and 3. This Phase II, randomised, double-blind, parallel-group study compared the efficacy of cediranib with placebo in patients with metastatic or recurrent clear cell renal cell carcinoma who had not previously received a VEGF signalling inhibitor. Methods: Patients were randomised (3:1) to cediranib 45 mg/day or placebo. The primary objective was comparison of change from baseline in tumour size after 12 weeks of therapy. Secondary objectives included response rate and duration, progression-free survival (PFS) and safety and tolerability. Patients in the placebo group could cross over to open-label cediranib at 12 weeks or earlier if their disease had progressed. This study has been completed and is registered with ClinicalTrials.gov, number NCT00423332. Findings: Patients (n = 71) were randomised to receive cediranib (n = 53) or placebo (n = 18). The primary study outcome revealed that, after 12 weeks of therapy, there was a significant difference in mean percentage change from baseline in tumour size between the cediranib (-20%) and placebo (+20%) arms (p < 0.0001). Eighteen patients (34%) on cediranib achieved a partial response and 25 (47%) experienced stable disease. Cediranib treatment prolonged PFS significantly compared with placebo (hazard ratio (HR) = 0.45, 90% confidence interval: 0.26-0.76, p = 0.017; median PFS 12.1 versus 2.8 months). The most common adverse events in patients receiving cediranib were diarrhoea (74%), hypertension (64%), fatigue (58%) and dysphonia (58%). Interpretation: Cediranib monotherapy demonstrated significant evidence of antitumour activity in patients with advanced renal cell carcinoma. The adverse event profile was consistent with previous studies of cediranib 45 mg. (C) 2011 Elsevier Ltd. All rights reserved.