The effect on pCR of bevacizumab and/or antimetabolites added to standard neoadjuvant chemotherapy: NSABP protocol B-40.

Abstract

LBA1005 Background: The addition of capecitabine (X), gemcitabine (G), and bevacizumab (B) to taxanes have each improved PFS in metastatic breast cancer. The primary aims of this trial were to determine if adding X or G to docetaxel (T) → AC will increase breast pathologic complete response (pCR) rates in operable, HER2-negative breast cancer and if adding B to T-based regimens →AC will increase pCR rates. Secondary aims included assessment of clinical complete response (cCR) rates. Methods: Pts received one of 3 T-based regimens, with or without B, 15mg/kg, q3wks x 4: 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, with or without B for the initial 2 cycles of AC. Pts randomized to B resumed B for 10 postop doses. The primary endpoint was pCR in the breast. The maximum of the standardized pairwise differences between pCR rate for the T → AC regimen and for the other 2 T-based regimens was used as the test statistic to adjust for multiple comparisons. Fisher’s exact test was used to compare the arms with and without B. Results: The groups were balanced, with 47% clinically node+, 56% poorly differentiated, and 59% HR+. Assessments for pCR were available from 1180 of 1206 randomized patients. pCR for TX and TG were 29.7% and 32% vs. 32.7% for T. Neither TX nor TG increased cCR rates relative to T (58.3% and 60.4% vs. 61.5%). TX and TG increased toxicity. Addition of B increased the pCR rate (28.4 vs. 34.5%, p=0.027) and the cCR rate (55.8 vs. 64.3%, p=0.007). The effect of B was predominantly in the HR+ subset (15.2 vs. 23.3%, p=0.008) with minimal effect in the HR- subset (47.3% vs. 51.3%, p=0.44). Grades 2/3/4 toxicities increased with B were HTN (1/<1/0% vs. 13/9/<1%), HFS (11/7/0% vs. 15/11/0%), and mucositis (10/3/0% vs. 20/5/0%). Conclusions: The addition of B to neoadjuvant chemotherapy improved pCR and cCR rates, but the addition of X or G to T did not improve outcomes. Follow-up for wound healing issues and DFS will help define the role of B in the treatment of early breast cancer. Funded by NCI PHS grants U10-CA-37377, U10-CA-69974, U10-CA-12027, U10-CA-69651, and U10-CA-44066, and F. Hoffmann La-Roche, Ltd., Genentech, USA, and Eli Lilly.