Benefit from next-generation ADT in AR-V7 positive patients.

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e16532 Background: AR-V7 status is considered a predictive biomarker for non-response to next generation androgen deprivation therapy (ADT) such as abiraterone and enzalutamide. We recently identified an AR-V7 positive patient who responded to Abiraterone. Thus, we hypothesized that a subgroup of patients might benefit from next generation ADT despite expression of AR-V7 in CTCs. Methods: We assessed biochemichal response and stable disease in our cohort of AR-V7 positive, castration resistant prostate cancer patients who had received therapy with abiraterone or enzalutamide (n = 21). CTC collection was performed before therapy initiation with either abiraterone (N = 11) or enzalutamide (N = 10). We defined benefit from therapy as either stable disease ( < 50% PSA decrease to < 25% PSA increase from PSA nadir), or biochemical response (PSA decrease > 50%). Results: Six out of 21 AR-V7 positive patients who had been treated with abiraterone or enzalutamide had a benefit from the therapy. Four patients even displayed a biochemical response with a PSA decrease between 60% and 80%. The progression free survival of the six patients was between 26 – 188 days. Characteristics of the six AR-V7 positive patients who experienced benefit from next generation ADT did not differ significantly from the 15 AR-V7 positive patients showing no biochemical response. However, only one of the 6 responders (16.7%) but 9 of the 15 non-responders (60%) had received next generation ADT prior to CTC collection and inclusion in our study Conclusions: When reviewing the cohort for AR-V7 positive patient who had a benefit from unmatched next generation ADT (defined as < 25% increase of PSA) we found 6 of 21 patients. The findings strongly argue that the current portrayal of AR-V7 status in the literature should not be directly translated into clinical decision making.

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