No Clinical Evidence for Increase in Tumour Malignant Potential in Patients (Pts) with Metastatic Breast Cancer (mBC) Treated with Bevacizumab (BV) and Docetaxel (D) in the Phase III AVADO Study.

Abstract

Abstract Background: The monoclonal antibody BV is directed against soluble VEGF and has shown significant clinical benefit when combined with chemotherapy in a range of tumour types, including in three phase III trials in mBC. Recent preclinical reports suggest that some anti-angiogenic agents (VEGFR tyrosine kinase inhibitors [TKIs] or VEGFR antibodies) increase the malignant potential of tumours (Pàez-Ribes; Ebos: Cancer Cell 2009:15). Although BV has a distinctly different mechanism of action, exploratory analyses to investigate those preclinical findings were performed on data from AVADO, a placebo (PL)-controlled study in first-line mBC.Methods: Pts received D (100mg/m2) q3w for up to 9 cycles, plus PL or BV (7.5 or 15mg/kg) q3w until disease progression (PD) or unacceptable toxicity. Mortality rates were calculated at 30-day intervals up to day 210 after discontinuation of PL or BV for any reason. For pts discontinuing PL or BV for toxicity, PFS was analysed using Kaplan-Meier methods. In the overall population, the proportion of pts with new metastatic lesions was analysed at PD.Results: As of 30 April 2009, 91 pts had discontinued PL or BV for toxicity; median PFS from discontinuation was longer in the BV arms than the PL arm. Mortality rates in pts stopping BV or PL for any reason (n=339) were similar or lower in the BV arms than the PL arm at all 30-day intervals for the first 210 days after discontinuation, the timeframe over which the analyses were performed. At PD, fewer BV than PL pts had developed new lesions. PL + DBV 7.5mg + DBV 15mg + DITT population, n241248247 Pts with PD, n (%)208 (86)212 (85)210 (85) Pts with PD & new lesion, n (%)160 (77)*154 (73)*138 (66)*All pts discontinuing BV or PL, n108118113 Mortality, n (%) Day 9028 (12)26 (11)15 (7) Day 15041 (18)38 (16)32 (15) Day 21053 (23)52 (23)45 (22)Pts discontinuing BV or PL for toxicity, n292735 PFS from discontinuation of BV or PL Median, months3.36.46.8 HR vs PL 0.710.73 [95% CI] [0.40–1.27][0.42–1.24]*% of pts with PDDiscussion: Although recent preclinical studies, carried out using agents targeting VEGF receptors, suggest that anti-angiogenic therapy increases tumour malignant potential, exploratory data from a large clinical trial of BV do not support this theory. PFS in AVADO was longer after discontinuation of BV than after discontinuation of PL. Mortality rates up to day 210 after PL/BV discontinuation were similar. The proportion of BV pts with new metastatic lesions at PD was lower than that of PL pts, suggesting that metastatic spread was not increased. Citation Information: Cancer Res 2009;69(24 Suppl):Abstract nr 6086.