Nab-paclitaxel plus bevacizumab in heavily pretreated HER2-negative metastatic breast cancer

Abstract

Background: Many agents have been used for the treatment of metastatic breast cancer (MBC) patients, including antitubulin drugs and antimetabolites, but none demonstrated a clear superiority. Furthermore, although some combinations of cytotoxic agents provide a small progression free survival (PFS) advantage, none showed an overall survival (OS) advantage, and toxicity is generally greater than for single agents. Therefore, at present, there is no standard for this treatment setting. New treatments that could delay disease progression without systemic toxicity would represent a significant advancement. In this regard, Nab-paclitaxel showed improved PFS and tolerability compared with standard cremophor-solubilized paclitaxel; based on this, we examined the efficacy and safety of combining weekly nab-paclitaxel and bevacizumab in patients with heavily treated MBC. The combination of bevacizumab with a taxane significantly improved progression-free survival (PFS) compared with taxane monotherapy in the first-line treatment of human epidermal growth factor receptor 2 (HER2)-negative MBC in a number of randomized, Phase III studies. Patients and methods: In this study, patients with HER2 negative MBC received Nab-paclitaxel 125 mg/m(2) intravenously on days 1, 8, 15, and bevacizumab (10 mg/ kg) intravenously on days 1 and 15 of a 28-day cycle. The primary end point was to assess the safety of this combination. Secondary end points included PFS and overall response rate (ORR). Results: From September 2014 to March 2015, 20 patients were enrolled in this trial. Median age was 53.0 (range, 30-76) years and all patients had received previous therapy. Median PFS was 9.2 months (95% confidence interval [CI], 7.8-25.1 months) and ORR was 85% (95% CI, 69%-95%) for the combination. The regimen was well tolerated with the most common grade 3/4 adverse events being neutropenia (75%) and thrombocytopenia (25%), and other serious events including 1 grade 3 and 1 grade 4 thrombotic event and 1 febrile neutropenia. Conclusion: The combination of nab-paclitaxel and bevacizumab for with HER2 negative MBC proved to be efficient and safe. Nab-paclitaxel can safely be offered to many women with MBC, with reasonable expectations of clinical benefit and without concern of significant toxicity. Nab-paclitaxel may be particularly beneficial for patients with aggressive disease, including those with mTNBC.