Study to Compare Alisertib With Paclitaxel vs. Paclitaxel Alone in Metastatic or Locally Recurrent Breast Cancer

The rationale behind assessing the effectiveness of the addition of alisertib to weekly paclitaxel therapy in patients with Triple Negative Breast Cancer and highly proliferative estrogen receptor-positive (ER+) and HER2- breast cancer is based on the unmet clinical need for effective strategies to prevent or delay resistance to taxane therapy in the metastatic setting. Synergistic or additive effects have been observed in breast cancer xenograft models which involved alisertib added to either paclitaxel or docetaxel. Alisertib inhibited the Pgp-mediated efflux of paclitaxel in a cell culture model. In addition, Aurora Kinase A is frequently overexpressed in Triple Negative Breast Cancer (TNBC), and expression levels have been shown to be prognostic in both of these breast cancer subtypes. The combination of alisertib with paclitaxel has also been investigated in a Phase 1 study in patients with locally advanced or metastatic ovarian and breast cancers, with preliminary evidence of activity in both tumor types including 6 partial response (PR)s and 3 stable disease (SD) in 11 patients with metastatic breast cancer.