A randomized, controlled, double-blind phase III study (AVOREN) of bevacizumab/interferon-α2a vs placebo/interferon- α2a as first-line therapy in metastatic renal cell carcinoma

Abstract

3 Background: Bevacizumab (BEV) is a monoclonal antibody that inhibits tumor angiogenesis by targeting VEGF. In relapsed RCC, BEV improved time to progression compared with placebo (2.5 vs. 4.8 months). A phase III trial was conducted to evaluate the efficacy and safety of BEV in combination with interferon (IFN)-a2a as first-line treatment in metastatic (m) RCC. The final analysis of progression-free survival (PFS) and interim analysis of overall survival (OS) are presented. Methods: Nephrectomized patients with clear cell mRCC, KPS of =70%, no CNS metastases and adequate organ function received IFN- a2a (x3/week at a recommended dose of 9 MIU for up to 1 year) plus BEV (10mg/kg q2w) or placebo until disease progression. Tumor assessments were performed every 8 weeks until week 32 and 12 weekly thereafter. Patients were stratified according to country and Motzer score. Results: Between June 2004 and October 2006, 649 patients were randomized (641 treated) at 101 centers in 18 countries. The treatment arms were well balanced for prognostic factors. At the data cutoff, 505 progression events had occurred, 111 patients remained on treatment, 287 had discontinued (discontinuations due to AEs were 12% with IFN vs. 28% with IFN-a2a/BEV), and 251 died. BEV-related side effects were generally mild and consistent with previous observations. The addition of BEV to IFN-a2a significantly increased PFS (10.2 vs. 5.4 mo) (HR=0.63; p<0.0001) and objective tumor response rate (30.6% vs. 12.4%; p<0.0001). A trend toward improved OS was observed with the addition of BEV to IFN-a2a (p=0.0670). Conclusions: BEV improves PFS when combined with IFN-a2a in mRCC. No unexpected safety events were observed. [Table: see text] [Table: see text]