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

Naoki Terada, Benjamin L. Maughan, Shusuke Akamatsu, Takashi Kobayashi, Toshinari Yamasaki, Takahiro Inoue, Tomomi Kamba, Osamu Ogawa, Emmanuel S. Antonarakis

Research output: Contribution to journalArticlepeer-review

48 Scopus citations


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.

Original languageEnglish (US)
Pages (from-to)441-448
Number of pages8
JournalInternational Journal of Urology
Issue number6
StatePublished - Jun 2017
Externally publishedYes

Bibliographical note

Funding Information:
The authors acknowledge the assistance of the following individuals in this study: Takehiko Segawa and Toru Yoshida, Kyoto City Hospital; Keiyu Matsumoto and Hiroshi Okuno, Kyoto Medical Center; Mitsuo Nonomura and Yoshiyuki Okada, Kyoto Katsura Hospital; Jin Yamada and Toru Kanno, Ijinkai Takeda Hospital; Tomoyuki Oida and Norio Kawase, Kosekai Takeda Hospital; Toshiya Akao and Noboru Shibasaki, Otowa Hospital; Keiji Ogura and Satoshi Ishitoya, Otsu Red Cross Hospital; Yasumasa Shichiri and Akihiro Hamada, Otsu Municipal Hospital; Hiroyuki Onishi and Koji Nishizawa, Shiga Medical Center for Adults; Kazuo Nishimura and Kazutoshi Okubo, Osaka Red Cross Hospital; Jun Takenawa, Takatsuki Red Cross Hospital; Hiroshi Kanamaru and Takeshi Soda, Kitano Hospital; Teruyoshi Aoyama and Kaoru Murakami, Kansai Electric Power Hospital; Mutsushi Kawakita and Takashi Matsuoka, Kobe City Medical Center General Hospital; Noriyuki Ito and Yosuke Shimizu, Nishikobe Medical Center; Yoji Taki, Jun Watanabe, Toyoka Public Hospital; Hiroshi Iwamura and Ayumu Matsuda, Hmeji Medical Center; Kazuhiro Okumura and Hiroaki Kawanishi, Tenri Hospital; and Tadashi Hayashi and Masahiro Tamaki, Japanese Red Cross Society Wakayama Medical Center.

Publisher Copyright:
© 2017 The Japanese Urological Association


  • abiraterone
  • castration resistant
  • enzalutamide
  • prostate cancer
  • sequential therapy


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