Enzalutamide Antitumour Activity Against Metastatic Castration-resistant Prostate Cancer Previously Treated with Docetaxel and Abiraterone: A Multicentre Analysis

Background: The degree of antitumour activity of enzalutamide following disease progression on docetaxel and abiraterone remains controversial. Objective: To examine the effect of enzalutamide in patients progressing following taxane-based chemotherapy and abiraterone. Design, setting, and participants: Metastatic castration-resistant prostate cancer patients entering one of four European compassionate use programmes of enzalutamide. Outcome measurements and statistical analysis: The primary end point was overall survival (OS). Secondary end points were association between OS and post-treatment prostate-specific antigen (PSA) kinetics, patient characteristics, and progression-free survival, respectively. Kaplan-Meier survival analysis and Cox proportional hazard analysis were performed. Results and limitations: We identified 137 patients who prior to enzalutamide had progressed following a median of eight cycles of docetaxel and seven courses of abiraterone. The median time on enzalutamide was 3.2 mo; median OS from the time patients started enzalutamide was 8.3 mo (95% confidence interval, 6.8-9.8). Only 45 (38%) and 22 (18%) patients had PSA declines (unconfirmed) > 30% and 50%, respectively. Patients who had more than 30% or 50% falls in PSA had improved survival compared with patients who had no such PSA fall (11.4 mo vs 7.1 mo; p = 0.001 and 12.6 vs 7.4 mo; p = 0.007, respectively). Poor performance status and low haemoglobin was negatively associated with OS. Conclusions: Median OS on enzalutamide following disease progression on taxane-based chemotherapy and abiraterone was modest, but patients who experience a PSA decline > 30% or 50%, respectively, with enzalutamide in this setting had longer survival. Patient summary: Enzalutamide produces modest prostate-specific antigen (PSA) responses in patients progressing following chemotherapy and abiraterone. Despite a modest PSA response, survival may still be improved. (C) 2014 European Association of Urology. Published by Elsevier B.V. All rights reserved.