ASCO GU 2017: Targeting reciprocal feed back inhibition: Apalutamide and everolimus in patients with metastatic castrate resistant prostate cancer - Poster Session Highlights

Orlando, Florida USA (UroToday.com) Studies of xenograft CRPC and PTEN deficient prostate cancer models have shown synergistic anti tumor activity of next generation anti-androgens such as apalutamide when combined with PI3K/mTOR inhibitors such as everolimus.



The primary hypothesis of this trial was that the combination of these drugs would overcome resistance to prior hormonal therapy with abiraterone (AA). Primary endpoint in mCRPC patients previously treated with AA was to determine safety, pharmakokinetics ( PK) and to recommend a phase 2 dose of the 2 drugs. Secondary endpoint was to evaluate anti tumor activity. 9 patients were enrolled. The PK for the combination was consistent with historical data of either drugs mono therapy. Most common side effect were fatigue (78%), diarrhea (56%). The median time on treatment was 26 weeks. 1 patient who was post abiraterone and enzalutamide remained on study for 66 weeks. PTEN deletion status did not correlate with time on study. PTEN status was unavailable in 1/3 of the patients. Although the combination of apalutamide and everolimus was safe and well tolerated, the treatment response was similar to data on AA following apalutamide alone. The trial was closed before expansion in favor of evaluating novel AR/PI3K pathway combinations in patients who have not yet been exposed to AA.

Presenter: Dana Rathkop, MSKCC, USA

Written By: Miki Haifler, MD, M.Sc, Fox Chase Cancer Center

at the 2017 Genitourinary Cancers Symposium - February 16 - 18, 2017 – Orlando, Florida USA