The Effect of Time to Castration Resistance on Outcomes With Abiraterone and Enzalutamide in Metastatic Prostate Cancer

Given the lack of predictive markers in prostate cancer, we questioned whether primary androgen deprivation therapy outcomes could predict the outcomes with subsequent novel androgen receptor-targeting therapies in a retrospective study of 80 patients. The primary androgen deprivation therapy response did not independently predict the outcomes to abiraterone and enzalutamide. Thus, further work is required to identify the predictive markers of benefit from novel androgen receptor-targeting therapies. Background: Abiraterone and enzalutamide are 2 novel androgen receptor (AR)-targeting therapies that improve survival in patients with metastatic castration-resistant prostate cancer. The factors that predict abiraterone and enzalutamide response are lacking. The objective of the present study was to determine whether the outcomes from primary androgen deprivation therapy (ADD could predict the outcomes with subsequent novel, AR -targeting therapies. Materials and Methods: We identified 80 consecutive patients with metastatic castration-resistant prostate cancer treated with abiraterone or enzalutamide. Cox regression models were used to analyze the relationships between the primary ADT response and the primary outcome of progression-free survival (PFS) after initiating novel hormonal therapy. The secondary outcomes included prostate-specific antigen decline and overall survival. The survival probabilities were plotted using the Kaplan-Meier method, and the differences assessed with the log-rank test. Results: The time to castration resistance with primary ADT showed a significant association with both PFS and overall survival after initiating novel hormone therapy (P = .032 and P = .028, respectively). Patients with progression during primary ADT before 1 year had a median PFS of 3.4 months compared with a median PFS of 7.6 and 8.1 months for patients whose time to castration resistance was >= 1 and <= 5 years (P = .008) and > 5 years (P = .026), respectively. However, the time to castration resistance was not an independent predictor of survival or the PSA response with novel AR-targeting therapy on multivariate analysis. Conclusion: A rapid time to progression during primary ADT was associated with poor outcomes but was not an independent predictor of the response to enzalutamide or abiraterone.