Bevacizumab (BV) maintenance therapy significantly delays disease progression (PD) or death compared with placebo (PL) in the AVADO trial (BV + docetaxel [D] vs D + PL in 1st-line HER2-negative locally recurrent [LR] or metastatic breast cancer [mBC]).

Abstract

#903 Background: BV (Avastin®) is a monoclonal antibody to VEGF that significantly improved PFS and response rate when combined with 1st-line taxane chemotherapy (CTx) in two randomised phase III studies in patients (pts) with LR or mBC: E2100 (weekly paclitaxel ± BV) and double-blind, PL-controlled study AVADO (D ± two different BV doses). Preclinical data suggest that BV inhibits tumour neovascularisation and can limit tumour vascular regrowth. Both above trial protocols recommended BV use until PD, even after discontinuation of concomitant CTx. In the NO16966 trial in metastatic colorectal cancer, PFS was longer for pts continuing BV following cessation of CTx than for those where BV and CTx were stopped at the same time. We report results of an exploratory analysis of time to PD or death after cessation of D in pts in AVADO.
 Methods: AVADO compared BV 7.5 or 15mg/kg + D 100mg/m2 with PL + D in 736 pts with inoperable LR or mBC, ECOG PS 0–1 and adequate LVEF. D and BV/PL were administered q3w, with D given for up to 9 cycles and BV/PL continued until PD or unacceptable toxicity.
 Results: The table presents median time from discontinuation of D until PD or death in different subgroups in the AVADO study. Approximately 70% of pts in each arm discontinuing D went on to receive at least one dose of BV or PL before PD.
 
 Conclusions: Continuation of single-agent BV at either dose after discontinuation of D significantly delayed PD or death compared with single-agent PL. These results support the hypothesis that BV may inhibit tumour neovascularisation and progression following CTx and suggests that clinical benefit may be maximised by treatment with BV until progression. Citation Information: Cancer Res 2009;69(2 Suppl):Abstract nr 903.

Angiogenesis as a therapeutic target in breast cancer

“…Preclinical studies have demonstrated rapid revascularization following early discontinuation of anti-VEGF treatment which might lead to re-growth of the tumor. Moreover, an exploratory analysis of the AVADO trial showed that maintenance use of bevacizumab after the discontinuation of docetaxel delayed progression of the disease, compared with placebo maintenance treatment [26].…”

Targeting Signal Transduction Pathways in Metastatic Breast Cancer: A Comprehensive Review

“…Based on the results from the AVADO trial, the existing EU label permitting the use of bevacizumab in combination with docetaxel was extended to allow bevacizumab to be combined with docetaxel, thus allowing additional patients access to bevacizumab treatment. Further analyses of the AVADO trial have revealed that treatment continuation with singleagent bevacizumab after discontinuation of docetaxel appears to delay disease progression [154], that there is no apparent correlation between the efficacy of bevacizumab plus docetaxel and hypertension or G-CSF use [155], and that the combination does not appear to be associated with a higher incidence of grade 3-5 bleeding events [156]. In summary, although bevacizumab has shown little activity as a single agent in MBC patients, combination therapy with chemotherapeutic agents has been associated with clinical activity in this patient population.…”

The Role of Targeted Agents in the Treatment of Metastatic Breast Cancer

“…fined. However, there is some evidence that the combination with the respective cytostatic agent should be switched to maintenance therapy with the VEGF antibody after 6-8 cycles, depending on the remission dynamics [7].…”