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

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/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.

Pazopanib Sensitivity in a Patient With Breast Cancer and FGFR1 Amplification

“…This subgroup has previously been shown to benefit from pazopanib treatment, 11 but biomarkers for response to this agent need to be identified, also because of toxicity concerns. 12 A promising biomarker for pazopanib and other FGFR inhibitors may be FGFR1 amplification, and in addition to the present case report, another recent publication reports stable disease in a patient with HR+ breast cancer with FGFR1 amplification. 13 Further potential markers for pazopanib treatment include alterations in other FGFR or FGFR ligand genes.…”

Vascular Endothelial Growth Factor Ligands and Receptors in Breast Cancer

“…Clinical studies for the efficacy of Sunitinib in breast cancer treatment were not satisfying so far [ 93 , 94 , 95 ]. The studies on Vandetanib, Axitinib, Pazopanib and Cediranib were also not relevant for a better treatment of breast cancer [ 96 , 97 , 98 ].…”

Targeting Angiogenesis in Breast Cancer: Current Evidence and Future Perspectives of Novel Anti-Angiogenic Approaches

“…The combination also had increased toxicity compared to lapatinib monotherapy (Cristofanilli et al, 2013;Johnston et al, 2013). The addition of pazopanib to chemotherapy in neoadjuvant treatment for HER2-negative locally advanced breast cancer was assessed in a phase II study, however substantial toxicity resulted in a high discontinuation rate of pazopanib (Tan et al, 2015).…”