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

• Published in: European urology 2015-08, Vol.68 (2), p.317-324
• Main Authors: Brasso, Klaus, Thomsen, Frederik B, Schrader, Andres J, Schmid, Sebastian C, Lorente, David, Retz, Margitta, Merseburger, Axel S, von Klot, Christoph A, Boegemann, Martin, de Bono, Johann
• Format: Article
• Language: English
• Subjects: Abiraterone; Aged; Aged, 80 and over; Androgen Antagonists - adverse effects; Androgen Antagonists - therapeutic use; Androstenes - adverse effects; Androstenes - therapeutic use; Antineoplastic Combined Chemotherapy Protocols - adverse effects; Antineoplastic Combined Chemotherapy Protocols - therapeutic use; Castration-resistant prostate cancer; Compassionate Use Trials; Disease Progression; Disease-Free Survival; Docetaxel; Drug Resistance, Neoplasm; Drug Substitution; Enzalutamide; Europe; Humans; Kallikreins - blood; Kaplan-Meier Estimate; Male; Middle Aged; Phenylthiohydantoin - adverse effects; Phenylthiohydantoin - analogs & derivatives; Phenylthiohydantoin - therapeutic use; Proportional Hazards Models; Prostate-Specific Antigen - blood; Prostatic Neoplasms, Castration-Resistant - blood; Prostatic Neoplasms, Castration-Resistant - drug therapy; Prostatic Neoplasms, Castration-Resistant - mortality; Prostatic Neoplasms, Castration-Resistant - pathology; PSA; Risk Factors; Survival; Taxoids - adverse effects; Taxoids - therapeutic use; Time Factors; Treatment Outcome; Urology
• ISSN: 0302-2838; 1873-7560
• DOI: 10.1016/j.eururo.2014.07.028

Abstract 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 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 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.