Toxicity Overrides Efficacy of Paclitaxel, Pazopanib for HER-Negative Breast Cancer

the Cancer Therapy Advisor take:

In a recent phase 2 single arm study conducted at multiple cancer centers, researchers sought to determine the effect of adding pazopanib to concurrent weekly paclitaxel after neoadjuvant therapy with doxorubicin and cyclophosphamide in human epidermal growth factor receptor (HER2)-negative locally advanced breast cancer (LABC).

The patients in the study had HER2-negative stage 3 breast cancer and were given 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. After surgery, patients received daily pazopanib for 6 months.

The study’s primary endpoint was breast and lymph node pathologic complete response. The study enrolled 101 patients with stage IIIA-C HER2-negative breast cancer between July 2009 and March 2011.

The pathologic complete response rate was 17% in evaluable patients who received paclitaxel and pazopanib, 9% in patients with hormone receptor-positive tumors, and 38% in patients with triple-negative tumors. Thirty-nine percent of patients received pazopanib before surgery.

During paclitaxel and pazopanib treatment the most frequent grade 3 and 4 adverse events were neutropenia (27%), diarrhea (5%), ALT and AST elevations (5%, respectively), and hypertension (5%).

Despite meeting the prespecified pathologic complete response rate for activity, the toxicity rates among patients was substantial and there was a high discontinuation rate of pazopanib; based on this researchers do not feel that further research in this drug combination is warranted.