Abstract PD2-1: The effect on overall and disease-free survival (OS & DFS) by adding bevacizumab and/or antimetabolites to standard neoadjuvant chemotherapy: NSABP Protocol B-40
Authors: Bear Harry D , Tang Gong , Rastogi Priya , Geyer Charles E , Liu Qing , Robidoux André , Atkins James N , Baez-Diaz Luis , Brufsky Adam M , Mehta Rita S , Fehrenbacher Louis , Young James A , Senecal Francis M , Gaur Rakesh , Margolese Richard G , Adams Paul T , Gross Howard M , Costantino Joseph P , Paik Soonmyung , Swain Sandra M , Mamounas Eleftherios P , Wolmark Norman 
Published: May 2015

Abstract
Purpose
The NSABP B-40 study was designed to determine whether the addition of capecitabine (X) or gemcitabine (G) to neoadjuvant docetaxel (T) followed by AC increased pathologic complete response (pCR) rates and improved outcomes of women with operable, HER2-negative breast cancer. In addition, B-40 was to determine whether the addition of neoadjuvant plus adjuvant bevacizumab (Bev) to T-based regimens followed by AC would increase pCR and improve outcomes. The pCR results and toxicities have been reported previously.
The DFS and OS results are reported here for the first time.
Methods
Patients (Pts) received one of three T-based regimens for 4 cycles: T 100 mg/m2 day 1; T 75 mg/m2 day 1 and X 825 mg/m2 BID days 1-14; or T 75 mg/m2 day 1 and G 1000 mg/m2 days 1 and 8. Pts then received preoperative AC x 4 cycles. Pts randomly assigned to the Bev groups received Bev at 15mg/kg, q3wks x 6 with the first 6 courses of neoadjuvant chemotherapy and were to resume Bev post-operatively for 10 doses. 1,206 pts were assigned and 1,163 of them were clinically eligible and had follow-up. The cutoff date for data presented here was March 31, 2014. The median follow-up was 4.7 years.
Results
Neither X nor G added to neoadjuvant chemotherapy increased DFS or OS. 50% of Bev pts for whom treatment data were available (577) completed 10 doses of post-op Bev; 26% did not start Bev post-op. Addition of Bev significantly increased OS (HR=0.70, p=0.01) and marginally increased DFS (HR=0.81, p=0.06). The effect of Bev was most notable in women with hormone receptor positive (HR+) breast cancers (DFS HR=0.71, p=0.04; OS HR=0.63, p=0.03).
Conclusions
Addition of G or X to neoadjuvant T + AC had no significant impact on DFS or OS. Bev added to neoadjuvant chemotherapy and continued post-operatively marginally increased DFS in the overall cohort, with a significant increase in DFS in the HR+ subset. The addition of bevacizumab significantly improved OS for women with operable HER-2-negative breast cancer. In agreement with previously reported results for pCR, the improvement in DFS and OS was seen preferentially in women with HR+ breast cancers.
Support
NCI PHS grants U10-CA-37377, -69974, -12027, -69651, -44066, and -44066-26, Genentech Inc, Roche Laboratories Inc, Eli Lilly, and Precision Therapeutics, Inc.
Citation Format: Harry D Bear, Gong Tang, Priya Rastogi, Charles E Geyer, Qing Liu, André Robidoux, James N Atkins, Luis Baez-Diaz, Adam M Brufsky, Rita S Mehta, Louis Fehrenbacher, James A Young, Francis M Senecal, Rakesh Gaur, Richard G Margolese, Paul T Adams, Howard M Gross, Joseph P Costantino, Soonmyung Paik, Sandra M Swain, Eleftherios P Mamounas, Norman Wolmark. The effect on overall and disease-free survival (OS & DFS) by adding bevacizumab and/or antimetabolites to standard neoadjuvant chemotherapy: NSABP Protocol B-40 [abstract]. In: Proceedings of the Thirty-Seventh Annual CTRC-AACR San Antonio Breast Cancer Symposium: 2014 Dec 9-13; San Antonio, TX. Philadelphia (PA): AACR; Cancer Res 2015;75(9 Suppl):Abstract nr PD2-1.