EXTH-22. THE CNS PENETRATING TAXANE TPI 287 AND THE AURKA INHIBITOR ALISERTIB IMPROVE SURVIVAL IN VIVO Free

Glioblastoma is the most common primary malignant brain tumor in adults and has a poor prognosis with current standard of care. The AURKA inhibitor alisertib exhibits antiproliferative activity against glioblastoma in vitro including our previous work. Unlike current clinically used taxane drugs, the novel taxane TPI 287 penetrates the CNS. In this study we stereotactically implanted human GB9 xenografts into nude mice brains and tested the activity of alisertib alone, TPI 287 alone and both together compared to control. Five days after implantation treatment was started using twice daily 20 mg/kg alisertib orally administered 5 days per week and/or 18 mg/kg TPI-287 administered intravenously every 4 days for a total of 3 treatments. Survival was assessed as well tumor volume using MR imaging at 2 weeks and 4 weeks after tumor implantation. Monotherapy with alisertib improved survival, which was further improved with the addition of TPI 287 (p=0.0058). TPI 287 alone did not significantly improve survival. Tumor volume was significantly decreased in all treatment groups at 2 weeks compared with control. At 4 weeks the alisertib and TPI 287 groups showed a trend toward decreased tumor volume with a significant decrease in the combination therapy group. This data supports the potential use of this combination therapy in human trials.