Safety of bevacizumab (BV) plus docetaxel (D) in patients (pts) with locally recurrent (LR) or metastatic breast cancer (mBC) who developed brain metastases during the AVADO phase III study.

Abstract

Abstract Abstract #4116 Background: BV (Avastin®) is a monoclonal antibody specific to VEGF. The randomised, double-blind AVADO study has demonstrated that two different BV doses combined with D significantly improved progression-free survival in pts with LR or mBC compared with D + placebo (PL); unstratified hazard ratio (HR) up to 0.72, stratified HR up to 0.61 censored for non-protocol therapy. BV combined with D did not result in increased risk of GI perforations, thromboembolic or bleeding events. Patients with CNS metastases are currently excluded from clinical trials with BV due to a potential risk of haemorrhage. This retrospective analysis investigated the adverse events (AEs) reported in pts who developed brain metastases while participating in the AVADO trial.
 Methods: The AVADO study compared D 100mg/m2 plus PL with D plus BV at either 7.5 or 15mg/kg in 736 pts with HER2-negative inoperable LR or mBC; no chemotherapy 6 months prior to randomisation (≥12 months if taxane-based); ECOG PS 0–1; adequate LVEF, and no CNS metastases at study entry. D was administered q3w for up to 9 cycles. BV/PL was administered q3w until disease progression or unacceptable toxicity.
 Results: Of the 730 pts in the safety population, a total of 24 pts developed brain metastases at some point during the AVADO trial. There was no difference in number of pts who developed brain metastases between trial arms. The mean time to development of brain metastases was 172 days with PL, 197 days with BV 7.5mg/kg and 242 days with BV 15mg/kg. One patient receiving BV 15mg/kg was diagnosed with brain metastases on Day 1 and excluded from the study. No CNS bleeding AEs were reported for pts with brain metastases and other grade 3–5 AEs in these pts occurred at a similar frequency in all trial arms.
 
 Conclusions: In concordance with the overall toxicity assessment, treatment with BV did not appear to be associated with CNS haemorrhage in pts with brain metastases. Frequency of grade 3–5 AEs was not increased in pts with brain metastases treated with BV compared with those treated with PL. Analysis of a larger dataset may provide further information on the safety of BV therapy in pts with brain metastases. Citation Information: Cancer Res 2009;69(2 Suppl):Abstract nr 4116.