Activity of sequential therapies (txs) in patients (pts) with castration resistant prostate cancer (CRPC) previously treated with galeterone

Background: Galeterone inhibits prostate cancer growth via: 1) irreversible and selective CYP17 inhibition, 2) competitive antagonism of the androgen receptor (AR), and 3) AR protein degradation. Developing a rational approach to sequential txs in CRPC is paramount to clinical decision making. The primary aim of this analysis is to evaluate clinical response and resistance to CRPC tx post galeterone. Methods: We conducted a retrospective analysis of men in ARMOR2 (NCT01709734 ), a phase II study designed to establish the dose of galeterone and assess safety and efficacy of the optimal dose (2550 mg daily). 39 men with treatment-naive CRPC from 6 sites are included in the post-galeterone tx analysis. We report on pts receiving galeterone at Partners Institutions (n=14). Subsequent analyses will include other sites. Results: For pts in the post-galeterone tx analysis (n=39), median age was 72 years (54 - 94) and median PSA was 16.8 ng/mL (3.3 - 634); 24 pts had metastases. Median time on galeterone was 119 days (11 - 392). Of the Partners pts (n=14), 9 discontinued tx: 3=AEs, 5=progression and 1=death. 8 pts received 1 and 2 received 2 post-galeterone txs. Median PSA at initiation of the first post-galeterone tx was 8.25 ng/mL (3.2 - 299). Median maximum percent PSA decline from initiation of first post-galeterone tx was 98% (range 100% decline, 33% increase, Table 1). Of the 2 pts who completed their first post-galeterone tx, duration of tx was 2 months (mos, enzalutamide) and 9 mos (docetaxel). Of the 6 pts still receiving their first post-galeterone tx, 3 have remained on tx for > 7 mos. Conclusions: Initial data indicates that pts may have favorable response to both hormonal tx and chemotherapy after galeterone with a lack of cross resistance. Additional analysis (available at ASCO) will expand these observations and provide useful insight for treating physicians. The predictive biomarker, AR-V7 is in Phase III development. (Table Presented).