Phase II study of neoadjuvant weekly nab-paclitaxel and carboplatin, with bevacizumab and trastuzumab, as treatment for women with locally advanced HER2+ breast cancer

Clin Breast Cancer. 2011 Oct;11(5):297-305. doi: 10.1016/j.clbc.2011.04.002. Epub 2011 May 5.


Purpose: Neoadjuvant treatment with chemotherapy plus trastuzumab is standard care for women with locally advanced, HER2-positive (HER2(+)) breast cancer. HER2 has been shown to stimulate angiogenesis through vascular endothelial growth factor upregulation. We investigated the feasibility and efficacy of bevacizumab in combination with trastuzumab, nab-paclitaxel, and carboplatin as neoadjuvant therapy for women with locally advanced HER2(+) breast cancer.

Patients and methods: Twenty-eight women with locally advanced HER2(+) breast cancer received nab-paclitaxel (100 mg/m(2) intravenously [I.V.] days 1,8, and 15) and carboplatin (AUC = 6 I.V. day 1) every 28 days × 6 cycles. Concurrent with chemotherapy, trastuzumab (4 mg/kg loading dose, then 2 mg/kg) and bevacizumab (5 mg/kg I.V.) were administered weekly × 23 weeks. Patients then underwent mastectomy or breast-conserving surgery; pathologic responses were assessed. After surgery, trastuzumab 6 mg/kg and bevacizumab 15 mg/kg were administered every 3 weeks (54 weeks total); locoregional radiotherapy and/or antiestrogen therapy was administered per standard guidelines.

Results: Twenty-six patients (90%) completed neoadjuvant therapy, with objective responses in 86%. Pathologic complete response (pCR) was confirmed in 14 of the 26 patients (54%) who had surgery. However, bevacizumab-related complications were common postoperatively and during adjuvant trastuzumab/bevacizumab therapy. Ten patients had wound-healing delays or infections (6 patients discontinued therapy); 4 patients had left ventricular ejection fraction (LVEF) decreases (1 patient discontinued therapy). Other severe treatment-related toxicity was uncommon. Only 9 patients (31%) completed all protocol therapy.

Conclusions: Neoadjuvant therapy with nab-paclitaxel, carboplatin, trastuzumab, and bevacizumab was feasible in most patients, producing a pCR rate comparable to that in chemotherapy/trastuzumab combinations. In contrast, prolonged bevacizumab/trastuzumab therapy after surgical treatment was not well tolerated, primarily due to bevacizumab-related toxicity. The role of bevacizumab in neoadjuvant therapy remains undefined.

Publication types

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

MeSH terms

  • Adult
  • Aged
  • Albumins / administration & dosage
  • Antibodies, Monoclonal, Humanized / administration & dosage
  • Antineoplastic Combined Chemotherapy Protocols / administration & dosage*
  • Antineoplastic Combined Chemotherapy Protocols / adverse effects
  • Bevacizumab
  • Breast Neoplasms / drug therapy*
  • Breast Neoplasms / metabolism
  • Breast Neoplasms / pathology
  • Carboplatin / administration & dosage
  • Female
  • Humans
  • Middle Aged
  • Neoadjuvant Therapy
  • Neoplasm Metastasis
  • Paclitaxel / administration & dosage
  • Receptor, ErbB-2*
  • Trastuzumab
  • Treatment Outcome
  • United States
  • Vascular Endothelial Growth Factor A / administration & dosage


  • 130-nm albumin-bound paclitaxel
  • Albumins
  • Antibodies, Monoclonal, Humanized
  • Vascular Endothelial Growth Factor A
  • Bevacizumab
  • Carboplatin
  • Receptor, ErbB-2
  • Trastuzumab
  • Paclitaxel