Does the combination of paclitaxel and alisertib improve the outcomes of patients with breast cancer?

The authors evaluated the safety and effectiveness of paclitaxel (Taxol) in combination with alisertib (MLN8237) for the treatment of advanced breast cancer (BC). The authors observed that a weekly, reduced dose of paclitaxel combined with alisertib improved the survival without cancer worsening in these patients.

Breast cancer (BC) can be classified depending on the presence of certain proteins on the surface of cancer cells. If BC cells express the HER2 protein on their surface, it is called HER2-positive BC, while it is called HER2-negative BC when HER2 is not present at all. In addition, some BCs might express hormone receptors on their surface. These BCs respond to female sex hormones such as estrogen or progesterone to grow. These are called estrogen receptor (ER) or progesterone receptor (PR)-positive. When cancer cells do not have any of these proteins on the cell surface, they are called triple-negative (TN) BC.

BCs might present an additional protein called AURKA, that promotes cancer growth. The presence of AUKRA protein has been linked with cancer recurrence after a short time and reduced survival. Alisertib is a drug able to block the function of AURKA protein. Experimental studies have shown good tumor response when adding alisertib to standard chemotherapy paclitaxel. However, it is not known whether the daily administration of alisertib in combination with paclitaxel is safe and effective in patients with advanced BC. 

This clinical trial included 174 women with advanced BC. These patients were randomly assigned to receive either paclitaxel alone (86) or paclitaxel plus alisertib (88). Patients had either TNBC or ER-positive, HER2-negative BC. Patients were followed up for an average of 22 months. 

In patients with ER-positive, HER2-negative BC, paclitaxel with alisertib significantly improved survival without cancer worsening (10.2 months) compared to paclitaxel alone (7.1 months). The addition of alisertib to paclitaxel treatment was associated with a 44% higher chance of cancer not worsening. After 1 year, it was estimated that 44% of patients in the combination group and 15.4% in the paclitaxel alone group would be alive without cancer worsening.

The average overall survival was similar in the combination group (26.3 months) and the paclitaxel alone group (25.1 months).

In patients with TNBC, the average survival without cancer worsening was also significantly longer in the combination group (9.6 months) compared to the paclitaxel alone group (5.7 months). The addition of alisertib to paclitaxel was associated with a 65% lower risk of cancer worsening in these patients. 

Most side effects in all patients were mild. Severe side effects that were more common in the combination group were low white and red blood cell counts, diarrhea, and sore gums.

The authors found that the combination of paclitaxel and alisertib improved survival without cancer worsening in patients with advanced BC with manageable side effects.

This study included a small number of participants and a short follow-up period. Further studies are needed to establish the benefit of this treatment combination. This trial was funded by Takeda, the manufacturer of alisertib.