Alisertib May Help Treat Neuroendocrine Prostate Cancer
Aurora kinase A inhibition with alisertib monotherapy may benefit a subset of patients with neuroendocrine prostate cancer.
Aurora kinase A inhibition with alisertib monotherapy may benefit a subset of patients with neuroendocrine prostate cancer (NEPC), according to a study presented at the European Society for Medical Oncology (ESMO) 2016 Congress.1
NEPC is an aggressive subtype of castration-resistant prostate cancer independent of androgen expression. Preclinical studies demonstrated that targeting Aurora A with alisertib blocks the interaction between Aurora A and N-myc, thereby suppressing NEPC signaling and tumor growth. Researchers evaluated the activity and tolerability of alisertib in this patient population.
For the multicenter, phase 2 trial (ClinicalTrials.gov Identifier: NCT01799278), researchers enrolled 59 patients with metastatic prostate cancer and NEPC morphology, greater than 50% IHC expression, new liver metastases without PSA progression, or greater than 3 to 5 times serum NSE/CgA.
Median progression-free survival was 8.7 weeks among the evaluable 56 patients treated with alisertib twice daily for 7 days of each 3-week cycle. The 6-month progression-free survival rate was 11.1% overall, but was 16.3% for pathologically defined NEPC. Median overall survival was 38 weeks.
Among the 17 patients with scans at cycle 3, median progression-free survival was 20 weeks and 6-month progression-free survival was 35.8%.
Two patients achieved exceptional response with complete resolution of liver metastases and a third patient had stable disease at 39 months of follow-up.
The findings suggest that alisertib may be beneficial in some patients, but integrating clinical, pathologic, and molecular features may help to improve patient selection.
- Beltran H, Danila D, Montgomery B, et al. A phase 2 study of the aurora kinase A inhibitor alisertib for patients with neuroendocrine prostate cancer (NEPC). Paper presented at: European Society for Medical Oncology (ESMO) 2016 Congress; October 7-11, 2016; Copenhagen, Denmark.