TBCRC 012: ABCDE, a phase II randomized study of adjuvant bevacizumab, metronomic chemotherapy (CM), diet and exercise after preoperative chemotherapy for breast cancer.

Abstract

TPS103 Background: Patients (pts) with residual breast cancer after neoadjuvant chemotherapy (C) are at increased risk of recurrence; no proven risk-reduction strategies exist, supporting exploration of novel therapies in the post-preoperative setting. Bevacizumab (B) combined with chemotherapy (C) has an established role in the treatment of metastatic disease; E5103 is exploring the efficacy of adjuvant combination C and B. DFCI 05-055 (Mayer et al, ASCO 2007, 2008) demonstrated the feasibility of 1 year B after preoperative C. Also, increasing data support risk reduction through lifestyle interventions. The ABCDE trial was designed to evaluate extended adjuvant B in a high risk cohort, in addition to assessing the contribution of exercise to a dietary intervention. Methods: Eligible pts have HER2- breast cancer and have received preop anthracycline and/or taxane with residual disease at surgery. Accrual goal is 660 pts, to begin 3/2010 within the Translational Breast Cancer Research Consortium. Acceptable stages include, for triple negative, preop stages I-III, or if ER/PR+, stage III preop or IIB postop. Therapy must be initiated between 28-180 days after last surgery. This is a 2 × 2 randomized study with a first randomization to 6 months (mo) B 15 mg/kg every 3 weeks (wks) plus 6 mo CM followed by 2.5 years B 15 mg/kg every 6-8 wks, versus observation, and a second randomization to a 1 year telephone-based lifestyle intervention, offering dietary modification alone, or in combination with a structured exercise program. Primary endpoint is recurrence-free survival at a median follow-up of 6 years; overall power is 0.80 to detect a hazard ratio of 0.59-0.68, depending on pt population. Correlative studies include B pharmacogenomics, evaluation of the impact of exercise on biomarkers associated with recurrence, exploration of tissue-based predictors of outcome, and prospective examination of cardiac toxicity. To our knowledge, this is the only trial testing a prolonged but less intensive adjuvant B schedule in high risk pts. Results of this study could have critical implications for the design of future clinical trials with antiangiogenic agents. Author Disclosure Employment or Leadership Position Consultant or Advisory Role Stock Ownership Honoraria Research Funding Expert Testimony Other Remuneration Genentech/Roche Genentech/Roche Genentech/Roche