Plasma AR status and cabazitaxel in heavily-treated metastatic castration-resistant prostate cancer (mCRPC)

203 Background: Plasma androgen receptor ( AR) copy number status has been identified as a potential biomarker of response in mCRPC patients receiving docetaxel or the AR-targeted therapies abiraterone or enzalutamide. However, the relevance of plasma AR status in the context of cabazitaxel therapy is unknown. Methods: Between September 2011 and January 2018, pre-therapy plasma samples were collected from 155 patients treated with second or third-line cabazitaxel at standard or reduced dose in different biomarker protocols. Droplet digital PCR was used to identify plasma AR gain and normal samples, with the primary objective to evaluate associations of plasma AR status with treatment outcome. In an exploratory analysis, a comparison between plasma AR status and treatment type was investigated by incorporating updated data from our prior study of 85 post-docetaxel patients receiving abiraterone or enzalutamide. Results: We observed a shorter median overall/progression-free survival (OS/PFS) in AR-gained compared to AR-normal patients (OS 10.5 versus 14.1 months, hazard ratio (HR) 1.44, 95% confidence interval (CI) 0.98-2.13, P = 0.064), and (PFS 4.0 versus 5.0 months, HR 1.47, 95%CI 1.05-2.07, P = 0.024). In mCRPC patients receiving second-line therapies, a significant treatment interaction was observed between plasma AR and cabazitaxel versus AR-directed therapies for OS (P = 0.041) but not PFS (P = 0.244). In an exploratory analysis, AR-gained patients treated with initial reduced-dose of cabazitaxel had a significantly shorter median OS (7.3 versus 11.5 months, HR 1.95, 95%CI 1.13-3.38, P = 0.016), and PFS (2.7 versus 5.0 months, HR 2.27, 95%CI 1.39-3.71, P = 0.001). Conclusions: Plasma AR status has a potential clinical utility in patients being considered for cabazitaxel. Validation of these findings in prospective trials are warranted.