Weekly paclitaxel and concurrent pazopanib following doxorubicin and cyclophosphamide as neoadjuvant therapy for HER-negative locally advanced breast cancer: NSABP Foundation FB-6, a phase II study

A. R. Tan, H. Johannes, P. Rastogi, S. A. Jacobs, A. Robidoux, P. J. Flynn, M. P. Thirlwell, L. Fehrenbacher, P. J. Stella, R. Goel, T. B. Julian, L. Provencher, M. J. Bury, K. Bhatt, C. E. Geyer, S. M. Swain, E. P. Mamounas, N. Wolmark

Research output: Contribution to journalArticle

8 Scopus citations

Abstract

This multicenter single-arm phase II study evaluated the addition of pazopanib to concurrent weekly paclitaxel following doxorubicin and cyclophosphamide as neoadjuvant therapy in human epidermal growth factor receptor (HER2)-negative locally advanced breast cancer (LABC). Patients with HER2-negative stage III breast cancer were treated with doxorubicin 60 mg/m2 and cyclophosphamide 600 mg/m2 for four cycles every 3 weeks followed by weekly paclitaxel 80 mg/m2 on days 1, 8, and 15 every 28 days for four cycles concurrently with pazopanib 800 mg orally daily prior to surgery. Post-operatively, pazopanib was given daily for 6 months. The primary endpoint was pathologic complete response (pCR) in the breast and lymph nodes. Between July 2009 and March 2011, 101 patients with stage IIIA–C HER2-negative breast cancer were enrolled. The pCR rate in evaluable patients who initiated paclitaxel and pazopanib was 17 % (16/93). The pCR rate was 9 % (6/67) in hormone receptor-positive tumors and 38 % (10/26) in triple-negative tumors. Pre-operative pazopanib was completed in only 39 % of patients. The most frequent grade 3 and 4 adverse events during paclitaxel and pazopanib were neutropenia (27 %), diarrhea (5 %), ALT and AST elevations (each 5 %), and hypertension (5 %). Although the pCR rate of paclitaxel and pazopanib following AC chemotherapy given as neoadjuvant therapy in women with LABC met the pre-specified criteria for activity, there was substantial toxicity, which led to a high discontinuation rate of pazopanib. The combination does not appear to warrant further evaluation in the neoadjuvant setting for breast cancer.

Original languageEnglish (US)
Pages (from-to)163-169
Number of pages7
JournalBreast Cancer Research and Treatment
Volume149
Issue number1
DOIs
StatePublished - Jan 1 2015

Keywords

  • Breast cancer
  • Neoadjuvant chemotherapy
  • Paclitaxel
  • Pazopanib

ASJC Scopus subject areas

  • Oncology
  • Cancer Research

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    Tan, A. R., Johannes, H., Rastogi, P., Jacobs, S. A., Robidoux, A., Flynn, P. J., Thirlwell, M. P., Fehrenbacher, L., Stella, P. J., Goel, R., Julian, T. B., Provencher, L., Bury, M. J., Bhatt, K., Geyer, C. E., Swain, S. M., Mamounas, E. P., & Wolmark, N. (2015). Weekly paclitaxel and concurrent pazopanib following doxorubicin and cyclophosphamide as neoadjuvant therapy for HER-negative locally advanced breast cancer: NSABP Foundation FB-6, a phase II study. Breast Cancer Research and Treatment, 149(1), 163-169. https://doi.org/10.1007/s10549-014-3221-2