High pathologic complete response in Her2-positive, early-stage breast cancer to a novel nonanthracycline neoadjuvant chemotherapy

Clin Breast Cancer. 2015 Feb;15(1):31-6. doi: 10.1016/j.clbc.2014.06.004. Epub 2014 Jun 24.

Abstract

Background: Neoadjuvant chemotherapy is widely used to downstage breast cancers before surgery and is an accepted standard of care among patients with early-stage breast cancer in whom adjuvant chemotherapy would be recommended. Pathologic complete response (pCR) rate is a robust predictor of outcome for certain breast cancer subtypes, including Her2-overexpressing breast cancer. The incorporation of Her2-targeted therapies has significantly increased the pCR rate in the neoadjuvant setting. Although regimens composed of trastuzumab, nab-paclitaxel, and vinorelbine have demonstrated clinical efficacy in patients with metastatic breast cancer, few studies have examined this combination in early-stage Her2+ breast cancer. We hypothesized that the combination of neoadjuvant nab-paclitaxel followed by vinorelbine could represent a nonanthracycline-based treatment option for early-stage Her2-overexpressing breast cancer.

Patients and methods: Patients received 4 cycles of nab-paclitaxel 260 mg/m(2) intravenously (IV) every 14 days for 4 cycles followed by vinorelbine 25 mg/m(2) IV weekly for 12 weeks with concurrent trastuzumab (4 mg/kg loading dose, and then 2 mg/kg/wk). The primary endpoint was the rate of pCR. Secondary endpoints included clinical response, toxicity, and survival rates.

Results: A total of 27 patients were accrued to the trial. The median tumor size was 4.0 cm, and more than 50% of patients had axillary lymph node involvement. The pCR rate was 48.1%. Among the 40% of patients who had hormone receptor-positive disease, the pCR rate was 18.2%, compared with 68.8% among patients with estrogen receptor/progesterone receptor-negative tumors.

Conclusions: The combination of trastuzumab with nab-paclitaxel followed by vinorelbine was well tolerated and had promising activity in the neoadjuvant setting.

Keywords: Breast cancer; Nab-paclitaxel; Neoadjuvant chemotherapy; Pathologic complete response; Trastuzumab.

Publication types

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

MeSH terms

  • Adult
  • Albumins / administration & dosage*
  • Albumins / adverse effects
  • Antibodies, Monoclonal, Humanized / administration & dosage*
  • Antibodies, Monoclonal, Humanized / adverse effects
  • Antineoplastic Combined Chemotherapy Protocols / therapeutic use*
  • Breast Neoplasms / drug therapy*
  • Breast Neoplasms / metabolism
  • Breast Neoplasms / mortality
  • Breast Neoplasms / pathology
  • Female
  • Humans
  • Middle Aged
  • Neoadjuvant Therapy
  • Neoplasm Staging
  • Paclitaxel / administration & dosage*
  • Paclitaxel / adverse effects
  • Receptor, ErbB-2 / metabolism
  • Recurrence
  • Remission Induction
  • Survival Analysis
  • Trastuzumab
  • Treatment Outcome
  • Vinblastine / administration & dosage
  • Vinblastine / adverse effects
  • Vinblastine / analogs & derivatives*
  • Vinorelbine

Substances

  • 130-nm albumin-bound paclitaxel
  • Albumins
  • Antibodies, Monoclonal, Humanized
  • Vinblastine
  • ERBB2 protein, human
  • Receptor, ErbB-2
  • Trastuzumab
  • Paclitaxel
  • Vinorelbine