Final Overall Survival (OS) Results from the Randomised, Double-Blind, Placebo-Controlled, Phase III AVADO Study of Bevacizumab (BV) Plus Docetaxel (D) Compared with Placebo (PL) Plus D for the First-Line Treatment of Locally Recurrent (LR) or Metastatic Breast Cancer (mBC).

Mature data from AVADO confirm the improvement in PFS and ORR with BV 15mg/kg combined with D compared with PL + D and suggest use of BV with 2nd-line therapy is a possible reason for lack of OS difference.

Abstract

Abstract Background: Anti-VEGF monoclonal antibody BV significantly improves efficacy in combination with standard therapies in multiple tumour types, with limited impact on toxicity. Three randomised phase III trials (E2100, AVADO and RIBBON-1) in mBC have demonstrated that BV + 1st-line chemotherapy (CTx) significantly improves progression-free survival (PFS) and overall response rates (ORR). We present mature OS data from AVADO.Methods: Patients (pts) with HER2-negative LR/mBC were randomised to D 100mg/m2 + PL, D + BV 7.5mg/kg or D + BV 15mg/kg. D was given q3w for ≤9 cycles. BV or PL was given q3w until disease progression/unacceptable toxicity. After progression, pts were offered BV with 2nd-line anticancer therapy in a post-study treatment phase. The primary endpoint was PFS; secondary endpoints included OS, time to treatment failure, ORR, duration of response and safety. An exploratory analysis conducted in pts receiving post-progression CTx compared OS in pts receiving 2nd-line BV with those who did not.Results: 736 pts were enrolled March 2006–April 2007. The primary analysis (data cut-off October 2007; median follow-up 10.2 months) showed significant improvements in PFS and ORR for both BV-containing arms compared with PL + D. Mature OS data (data cut-off April 2009; median follow-up 25 months) are shown (Table). There was no difference in median OS between the study arms (range 30–32 months). Recognising the limitations of the non-randomised comparison in exploratory analyses, results suggest that use of BV with 2nd-line therapy is a possible reason for lack of OS difference. Updated PFS and ORR were superior for the 15mg/kg BV arm compared with PL + D. Results for the 7.5mg/kg BV arm also indicated a, less pronounced, treatment benefit. BV had limited impact on the safety profile of docetaxel. Increased SAEs in the 15mg/kg BV arm may be due to more pts receiving 9 cycles of D than in the PL arm (51% vs 42%).Conclusions: There was no difference in OS between study arms. Exploratory analyses suggest that use of 2nd-line BV with CTx may influence OS. These mature data confirm the improvement in PFS and ORR with BV 15mg/kg combined with D compared with PL + D. Citation Information: Cancer Res 2009;69(24 Suppl):Abstract nr 41.