OT3-02-04: TBCRC 012: ABCDE, a Phase II Randomized Study of Adjuvant Bevacizumab, Metronomic Chemotherapy (CM), Diet and Exercise after Preoperative Chemotherapy for Breast Cancer.
Authors: Mayer EL , Ligibel JA , Burstein HJ , Peppercorn JM , Miller KD , Carey LA , Dickler MN , Mayer IA , Forero A , Eng-Wong J , Pletcher PJ , Ryabin N , Gelman R , Wolff AC , Winer EP 
Published: June 2012

Abstract
Background Patients (pts) with residual breast cancer after neoadjuvant chemotherapy 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 is active in metastatic disease; ongoing studies are exploring the efficacy of adjuvant combination chemotherapy and B. DFCI 05–055 (Mayer et al, ASCO 2007, 2008) demonstrated the feasibility of 1 year B after preoperative chemotherapy. Also, increasing data support risk reduction through lifestyle interventions (Segal, Ligibel et al, ASCO 2011). The ABCDE trial was designed to evaluate extended adjuvant B in a high risk post-preoperative cohort, and also assess the contribution of exercise to a dietary intervention.
Eligibility Criteria Eligible pts have HER2− breast cancer and have received preoperative anthracycline and/or taxane-based chemotherapy with residual invasive disease at surgery. Acceptable stages include: triple negative if preop stages I-III, or ER+/PR+ if stage III preop or IIB postop. Acceptable organ function and standard B exclusions apply. Registration must occur between 28–180 days after last surgery.
Specific Aims Primary endpoint is recurrence-free survival at a median follow-up of 6 years. Secondary endpoints include B pharmacogenomics, evaluation of the impact of exercise on quality of life and biomarkers associated with recurrence, and prospective examination of cardiac toxicity. Residual tissue-based predictors of outcome will be extensively explored, including PAM50, Ki67, and VEGF hypoxia signature.
Methods 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 (C 50 mg daily, M 2.5 mg twice daily days 1, 2 each wk), followed by 2.5 years B 15 mg/kg every 6–8 wks, versus observation. A second randomization is to a 1 year telephone-based lifestyle intervention, offering dietary modification alone, or in combination with a structured exercise program.
Statistical Methods and Accrual Total sample size is 660 pts within the Translational Breast Cancer Research Consortium. Overall power is 0.80 to detect a hazard ratio of 0.59−0.68, depending on pt population. Accrual initiated early 2011 and is expected to continue for the next 36 months.
Conclusions Patients with residual disease after preoperative chemotherapy are at high risk of recurrence and have unmet medical needs. To our knowledge, this is the only trial testing a prolonged but less intensive adjuvant B schedule in this clinical setting. Results of this study could have critical implications for the management of this patient population and for the design of future clinical trials with anti-angiogenic agents.
Citation Information: Cancer Res 2011;71(24 Suppl):Abstract nr OT3-02-04.