Neoadjuvant bevacizumab, docetaxel and capecitabine combination therapy for HER2/neu-negative invasive breast cancer: Efficacy and safety in a phase II pilot study

Eur J Surg Oncol. 2009 Oct;35(10):1048-54. doi: 10.1016/j.ejso.2009.01.014. Epub 2009 Feb 27.

Abstract

Purpose: To evaluate the triplet combination of bevacizumab, capecitabine and docetaxel (XTA) as neoadjuvant therapy for breast cancer.

Experimental design: Patients with invasive, HER2-negative, nonmetastatic breast cancer (T2-4c >2cm) and no prior systemic therapy received six 21-day cycles of XTA (bevacizumab 15mg/kg, day 1, cycles 1-5; docetaxel 75mg/m(2), day 1 of each cycle; capecitabine 950mg/m(2) twice daily for 14 days of each cycle). Patients underwent surgery 2-4 weeks after completing XTA, followed by radiotherapy, chemotherapy and hormone therapy according to institution guidelines. Pathologic complete response (pCR), the primary endpoint, was defined as no evidence of invasive tumour in the final surgical sample. Secondary endpoints included rates of clinical response and breast-conserving surgery and safety.

Results: Median age of the 18 enrolled patients was 48 years (range 34-69). Most patients (72%) received six cycles of neoadjuvant therapy. pCR rate was 22% (95% confidence interval [CI]: 6-48). Nine of the patients without pCR achieved clinical partial response, giving a 72% overall clinical response rate (95% CI: 47-90). Fifteen patients underwent breast-conserving surgery (83%; 95% CI: 59-96). One additional patient had breast-conserving surgery, followed by mastectomy 1 month later. The remaining 2 patients underwent modified radical mastectomy. XTA was reasonably well tolerated, with no unexpected toxicities or treatment-related deaths.

Conclusions: The 22% pCR rate in a HER2-negative population suggests that addition of bevacizumab increases the activity of neoadjuvant capecitabine-docetaxel. Further evaluation of this regimen in early breast cancer is recommended.

Publication types

  • Clinical Trial, Phase II
  • Research Support, Non-U.S. Gov't

MeSH terms

  • Adult
  • Aged
  • Angiogenesis Inhibitors / administration & dosage
  • Angiogenesis Inhibitors / adverse effects
  • Antibodies, Monoclonal / administration & dosage
  • Antibodies, Monoclonal / adverse effects
  • Antibodies, Monoclonal, Humanized
  • Antineoplastic Combined Chemotherapy Protocols / adverse effects
  • Antineoplastic Combined Chemotherapy Protocols / therapeutic use*
  • Bevacizumab
  • Breast Neoplasms / drug therapy*
  • Breast Neoplasms / metabolism
  • Capecitabine
  • Deoxycytidine / administration & dosage
  • Deoxycytidine / adverse effects
  • Deoxycytidine / analogs & derivatives
  • Docetaxel
  • Drug-Related Side Effects and Adverse Reactions
  • Female
  • Fluorouracil / administration & dosage
  • Fluorouracil / adverse effects
  • Fluorouracil / analogs & derivatives
  • Humans
  • Middle Aged
  • Neoadjuvant Therapy
  • Pilot Projects
  • Receptor, ErbB-2 / metabolism
  • Taxoids / administration & dosage
  • Taxoids / adverse effects

Substances

  • Angiogenesis Inhibitors
  • Antibodies, Monoclonal
  • Antibodies, Monoclonal, Humanized
  • Taxoids
  • Deoxycytidine
  • Docetaxel
  • Bevacizumab
  • Capecitabine
  • Receptor, ErbB-2
  • Fluorouracil