Aflibercept versus placebo in combination with docetaxel/prednisone for first-line treatment of men with metastatic castration-resistant prostate cancer (mCRPC): Results from the multinational phase III trial (VENICE).

Abstract

13 Background: Docetaxel/prednisone is standard first-line chemotherapy for mCRPC. Aflibercept (known as ziv-aflibercept in the US) is a recombinant human fusion protein that binds VEGF-A, VEGF-B and Placental Growth Factor (PlGF), thereby inhibiting angiogenesis. Methods: VENICE was a double-blind, randomized phase III study with overall survival (OS) as primary endpoint. Men with mCRPC, ECOG PS 0-2, adequate organ function and no prior cytotoxic therapy were treated with docetaxel (75 mg/m² iv q3w) and oral prednisone (5mg bid) and randomized double blind 1:1 to receive aflibercept (A) 6 mg/kg or placebo (Pbo), IV every 3 weeks. Pts were stratified by ECOG PS (0-1 vs 2). For final OS analysis, 873 deaths were required to detect a hazard ratio (HR) of 0.8 with 90% power (overall 2-sided α = 0.05). Results: From Aug 2007 to Feb 2010, 1224 patients (median age 68 yr, PS 0-1 96%) were randomized. Baseline characteristics were well balanced between arms. Median number of cycles was 8 (A) and 9 (Pbo). Median relative dose intensity was >0.93 for A, Pbo and docetaxel. At final cut-off, median follow-up was 35.4 mos and 873 pts had died. Results for primary and key secondary endpoints with confidence intervals are in the table. Higher incidence of all grade hypertension, stomatitis, appetite disorders, diarrhea, dehydration, epistaxis, dysphonia, cough, headache and infections was observed in the aflibercept arm. Conclusions: Aflibercept in combination with docetaxel/prednisone given as first line chemotherapy for mCRPC did not lead to a statistically significant improvement in OS and added toxicity. (NCT00519285 sponsored by Sanofi and Regeneron Pharmaceuticals, Inc.) Clinical trial information: NCT00519285. [Table: see text]