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

BackgroundThe degree of antitumour activity of enzalutamide following disease progression on docetaxel and abiraterone remains controversial.ObjectiveTo examine the effect of enzalutamide in patients progressing following taxane-based chemotherapy and abiraterone.Design, setting, and participantsMetastatic castration-resistant prostate cancer patients entering one of four European compassionate use programmes of enzalutamide.Outcome measurements and statistical analysisThe primary end point was overall survival (OS). Secondary end points were association between OS and posttreatment 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 limitationsWe 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.ConclusionsMedian 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 summaryEnzalutamide produces modest prostate-specific antigen (PSA) responses in patients progressing following chemotherapy and abiraterone. Despite a modest PSA response, survival may still be improved.