A randomized, double-blind, placebo-controlled phase III trial comparing docetaxel, prednisone, and placebo with docetaxel, prednisone, and bevacizumab in men with metastatic castration-resistant prostate cancer (mCRPC): Survival results of CALGB 90401.

Abstract

LBA4511 Background: The preclinical activity of vascular endothelial growth factor (VEGF) blockade, the inverse relationship of plasma and urine VEGF levels and survival in mCRPC patients (pts), and encouraging phase II data testing estramustine and docetaxel with bevacizumab suggested that VEGF blockade was an appropriate potential strategy in mCRPC. A phase III study testing the effect of adding bevacizumab to standard docetaxel and prednisone therapy administered every 3 weeks in pts with mCRPC was conducted. Methods: 1050 pts with chemotherapy naïve, mCRPC with evidence of progressive disease despite castrate testosterone levels and anti-androgen withdrawal, ECOG performance status ≤ 2, and adequate bone marrow, hepatic and renal function were eligible. Pts were prospectively randomized with equal probability to receive docetaxel (D:75 mg/m2 IV over 1 hour q 21 days), plus prednisone (P) 5 mg po BID with either bevacizumab (B:15 mg/kg given intravenously q 3 weeks following D) or placebo. All patients received dexamethasone 8 mg PO 12, 3 and 1 hour prior to D. Randomization was stratified by predicted 24 mo survival probability, age and history of prior arterial thrombotic event. The primary endpoint was overall survival (OS). The trial was designed with 86% power to detect a 21% decrease in the hazard rate of death (equivalent to an increase in median OS from 19 months to 24 months) assuming a two-sided significance level of 0.05. The primary analysis was based on the stratified log-rank statistic adjusted for the stratification factors following observation of 748 deaths. Results: See Table . Conclusions: Despite an improvement in PFS, measurable disease response and post-therapy PSA decline, the addition of bevacizumab to docetaxel and prednisone did not improve OS in men with mCRPC, and was associated with greater morbidity and mortality. The median OS of pts treated with standard DP (21.5 m) was longer than previously reported (19 m). [Table: see text] [Table: see text]