NSABP B-40 Trial

Recognizing that bevacizumab, capecitabine, and gemcitabine:
- Have been shown to improve outcomes when added to taxanes in patients with metastatic breast cancer:
  - The NSABP B-40 trial:
    - Was designed to determine whether adding capecitabine or gemcitabine to docetaxel, followed by anthracycline doxorubicin and cyclophosphamide (AC):
      - Would improve the outcomes in patients with operable, HER2-negative breast cancer
  - The trial also sought to determine the effect of adding bevacizumab to these neoadjuvant chemotherapy regimens
  - Patients were divided into three groups:
    - Docetaxel followed by AC
    - Docetaxel and capecitabine followed by AC
    - Docetaxel plus gemcitabine followed by AC
    - Each of these three groups was then randomized to receive:
      - Bevacizumab with the first 6 cycles of chemotherapy or not, for a total of 6 treatment arm
    - The addition of capecitabine or gemcitabine to docetaxel therapy, compared to docetaxel alone:
      - Did not significantly increase the rate of pCR:
        
        29.7% and 31.8%, respectively, vs 32.7%; P=0.69
      - Both capecitabine and gemcitabine were associated with:
        
        Increased toxic side effects such as hand-foot syndrome, mucositis, and neutropenia
    - However, the addition of bevacizumab significantly increased the rate of pCR in the breast:
      - From 28.2% to 34.5% (P=0.02):
        
        This effect was more pronounced in the hormone receptor-positive subset of patients:
        
        15.1% pCR without bevacizumab vs 23.2% with bevacizumab:
        
        However, the addition of bevacizumab also increased rates of hypertension, left ventricular systolic dysfunction, hand-foot syndrome, and mucositis
References:
- Bear HD, Tang G, Rastogi P, Geyer Jr CE, Robidoux A, Atkins JN, et al. Bevacizumab added to neoadjuvant chemotherapy for breast cancer. N Engl J Med. 2012;366(4):310-320.
- NSABP clinical trials overview. Protocol B-40. A randomized phase III trial of neoadjuvant therapy in patients with palpable and operable breast cancer evaluating the effect on pathologic complete response (pCR) of adding capecitabine or gemcitabine to docetaxel when administered before AC with or without bevacizumab and correlative science studies attempting to identify predictors of high likelihood for pCR with each of the regimens. National Surgical Adjuvant Breast and Bowel Project website. http://www.nsabp.pitt.edu/B-40.asp. Accessed May 15, 2020