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

Int J Urol. 2017 Jun;24(6):441-448. doi: 10.1111/iju.13346. Epub 2017 Apr 28.

Abstract

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.

Keywords: abiraterone; castration resistant; enzalutamide; prostate cancer; sequential therapy.

Publication types

  • Comparative Study
  • Multicenter Study

MeSH terms

  • Androstenes / administration & dosage*
  • Antineoplastic Combined Chemotherapy Protocols / administration & dosage*
  • Baltimore
  • Benzamides
  • Disease Progression
  • Drug Administration Schedule
  • Humans
  • International Cooperation
  • Japan
  • Kallikreins / blood
  • Male
  • Neoplasm Grading
  • Nitriles
  • Phenylthiohydantoin / administration & dosage
  • Phenylthiohydantoin / analogs & derivatives*
  • Progression-Free Survival
  • 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
  • Retrospective Studies
  • Survival Analysis
  • Time Factors

Substances

  • Androstenes
  • Benzamides
  • Nitriles
  • Phenylthiohydantoin
  • enzalutamide
  • KLK3 protein, human
  • Kallikreins
  • Prostate-Specific Antigen
  • abiraterone