NSABP B-40

  • 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 the anthracycline doxorubicin and cyclophosphamide (AC):
      • Would improve the outcomes in patients with operable, HER2-negative breast cancer
    • It was also designed 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 six cycles of chemotherapy or not:
        • For a total of six treatment arms
  • 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 drugs 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, the hand-foot syndrome, and mucositis
  • References:
    • Bear HD, Tang G, Rastogi P, et al. Bevacizumab added to neoadjuvant chemotherapy for breast cancer. N Engl J Med. 2012;366:310-320.
    • 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. http://www.nsabp.pitt.edu/B-40.asp. Accessed December 18, 2016.