Details

Autor(en) / Beteiligte

• 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.

Titel

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

Ist Teil von

• Breast cancer research and treatment, 2015-01, Vol.149 (1), p.163-169

Ort / Verlag

Boston: Springer US

Erscheinungsjahr

2015

Quelle

MEDLINE

Beschreibungen/Notizen

• 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/m 2 and cyclophosphamide 600 mg/m 2 for four cycles every 3 weeks followed by weekly paclitaxel 80 mg/m 2 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.