title: Phase II study of neoadjuvant weekly nab-paclitaxel and carboplatin, with bevacizumab and trastuzumab, as treatment for women with locally advanced HER2+ breast cancer.
abstract: OBJECTIVE
  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.
  
  
  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.
authors: Sarah Cannon Research Institute, Nashville, TN 37203, USA.
authors: Denise A
authors: DA
authors: Yardley
authors: Eric
authors: E
authors: Raefsky
authors: Raul
authors: R
authors: Castillo
authors: Anup
authors: A
authors: Lahiry
authors: Richard
authors: R
authors: Locicero
authors: Dana
authors: D
authors: Thompson
authors: Mythili
authors: M
authors: Shastry
authors: Howard A
authors: HA
authors: Burris
authors: John D
authors: JD
authors: Hainsworth
mesh_terms: D000328:Adult; D000368:Aged; D000418:Albumins / Q000008:administration & dosage; D061067:Antibodies, Monoclonal, Humanized / Q000008:administration & dosage; D000971:Antineoplastic Combined Chemotherapy Protocols / Q000008:administration & dosage* / Q000009:adverse effects; D000068258:Bevacizumab; D001943:Breast Neoplasms / Q000188:drug therapy* / Q000378:metabolism / Q000473:pathology; D016190:Carboplatin / Q000008:administration & dosage; D005260:Female; D006801:Humans; D008875:Middle Aged; D020360:Neoadjuvant Therapy; D009362:Neoplasm Metastasis; D017239:Paclitaxel / Q000008:administration & dosage; D018719:Erb-b2 Receptor Tyrosine Kinases; D000068878:Trastuzumab; D016896:Treatment Outcome; D014481:United States; D042461:Vascular Endothelial Growth Factor A / Q000008:administration & dosage
chemical_list: D000418:Albumins; D061067:Antibodies, Monoclonal, Humanized; D000068258:Bevacizumab; D016190:Carboplatin; D017239:Paclitaxel; D018719:Erb-b2 Receptor Tyrosine Kinases; D000068878:Trastuzumab; D042461:Vascular Endothelial Growth Factor A; C520255:130-nm albumin-bound paclitaxel