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.
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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.
RELATED: Metastasis-free Survival: a Surrogate for OS in Localized Prostate Cancer
The findings suggest that alisertib may be beneficial in some patients, but integrating clinical, pathologic, and molecular features may help to improve patient selection.
Reference
- 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.
