Exploring the optimal sequence of abiraterone and enzalutamide in patients with chemotherapy-naïve castration-resistant prostate cancer: The Kyoto-Baltimore collaboration.

OBJECTIVES

To evaluate and compare the efficacy of sequential treatment with abiraterone followed by enzalutamide or vice versa for castration-resistant prostate cancer.

METHODS

We retrospectively evaluated data on 198 consecutive chemotherapy-naïve patients who had received both abiraterone and enzalutamide for castration-resistant prostate cancer at Kyoto University Hospital (including satellite hospitals) and at Johns Hopkins Cancer Center. Prostate-specific antigen progression-free survival and overall survival in patients treated with sequential abiraterone-to-enzalutamide versus enzalutamide-to-abiraterone without intervening therapies were compared.

RESULTS

Overall, 113 patients were treated with the abiraterone-to-enzalutamide sequence and 85 with the enzalutamide-to-abiraterone sequence. Median prostate-specific antigen progression-free survival was not significantly different between abiraterone and enzalutamide in the first-line setting (hazard ratio 0.88, 95% confidence interval 0.66-1.19, P = 0.412), but there was an advantage favoring enzalutamide compared with abiraterone in the second-line setting (hazard ratio 0.67, 95% confidence interval 0.49-0.91, P = 0.009). Furthermore, the combined prostate-specific antigen progression-free survival was significantly longer in the abiraterone-to-enzalutamide sequence than in the enzalutamide-to-abiraterone sequence (hazard ratio 0.56, 95% confidence interval 0.41-0.76, P < 0.001). The difference was significant even in multivariate analyses (hazard ratio 0.65, 95% confidence interval 0.42-0.99, P = 0.044). There was no statistical difference in overall survival between the two sequences in univariate (hazard ratio 0.88, 95% confidence interval 0.53-1.43, P = 0.599) and multivariate analyses (hazard ratio 0.81, 95% confidence interval 0.49-1.35, P = 0.427).

CONCLUSIONS

The abiraterone-to-enzalutamide sequence might have more favorable efficacy in terms of combined prostate-specific antigen progression-free survival than the enzalutamide-to-abiraterone sequence, although no differences in overall survival were observed. This could possibly be attributable to longer prostate-specific antigen progression-free survival with second-line enzalutamide compared with abiraterone.