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A randomized, double-blind, comparison of radium-223 and placebo, in combination with abiraterone acetate and prednisolone, in castration-resistant metastatic prostate cancer: subgroup analysis of Japanese patients in the ERA 223 study

Abstract

Background

ERA 223 compared concurrent abiraterone acetate/prednisolone (AAP) plus radium-223 with AAP plus placebo in men with chemotherapy-naïve asymptomatic or mildly symptomatic metastatic castration-resistant prostate cancer (mCRPC) and bone metastases. We report data from a subgroup of Japanese patients in ERA 223.

Methods

Patients were randomized to radium-223 (55 kBq/kg) or placebo once every 4 weeks (max. 6 cycles), and also received oral abiraterone acetate 1000 mg once daily plus prednisone/prednisolone 5 mg twice daily during and after radium-223/placebo treatment, until a symptomatic skeletal event (SSE). The primary endpoint was SSE-free survival (SSE-FS); overall survival (OS) was a secondary endpoint.

Results

Of 806 patients randomized in ERA 223, 114 patients (57 per arm) were enrolled in Japan. SSE-FS was not improved significantly in the radium-223 arm [25.5 months, 95% CI 20.6–not estimated (NE)] compared with the placebo arm (28.7 months, 95% CI 19.7–NE) (HR = 0.907, 95% CI 0.501–1.642). OS and other secondary endpoints were not improved significantly in the radium-223 arm. The incidence of fracture was 23% and 11% in the radium-223 and placebo arms, respectively. The incidence of death was 32% and 36%, respectively.

Conclusions

In the Japanese ERA 223 subgroup, concurrent treatment with AAP and radium-223 did not significantly improve SSE-FS and increased the incidence of fracture, similar to outcomes achieved in the overall population, while an increased incidence of death was not evident. The combination of radium-223 with AAP is not recommended in Japanese patients with asymptomatic or mildly symptomatic mCRPC and bone metastases.

Clinical trial registration

Clinical trial registration no: NCT02043678.

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Acknowledgements

The authors thank the patients who participated in the study and the staff at the participating centers who made the study possible. Professional medical writing support was provided, under the guidance of the authors and in line with GPP-3 guidelines, by David P. Figgitt PhD, ISMPP CMPP™ and Stephen P. Clissold, PhD, ISMPP CMPP™, Content Ed Net, with funding from Bayer. Investigators in Japan who participated in the study and are not listed as authors are Satoshi Fukasawa (Department of Urology/Prostate Cancer, Chiba Cancer Center), Masashi Kato (Department of Urology, Nagoya University Graduate School of Medicine), Yoshiyuki Miyaji (Department of Urology, Kawasaki Medical School), Yoshiaki Wakumoto (Department of Urology, Juntendo University Graduate School of Medicine), Takeshi Kishida (Department of Urology, Kanagawa Cancer Center), Hideki Sakai (Department of Urology, Nagasaki University Graduate School of Biomedical Sciences), Takayuki Sugiyama (Department of Urology, Hamamatsu University School of Medicine), Katsuyoshi Hashine (Department of Urology, National Hospital Organization Shikoku Cancer Center), Yoshihide Kawasaki (Department of Urology, Tohoku University Graduate School of Medicine), Yasuhiro Hashimoto (Department of Urology, Hirosaki University Graduate School of Medicine), Tomohiko Ichikawa (Department of Urology, Chiba University), Mutsushi Kawakita (Department of Urology, Kobe City Medical Center General Hospital), Toshiyuki Kamoto (Department of Urology, Faculty of Medicine, University of Miyazaki), Masaki Shiota (Department of Urology, Graduate School of Medical Sciences, Kyushu University), Junji Yonese (Department of Urology, Cancer Institute Hospital, Japanese Foundation for Cancer Research), Teruyuki Ogawa (Department of Urology, Shinshu University School of Medicine), Takeo Kosaka (Department of Urology, Keio University School of Medicine), Hideyasu Matsuyama (Department of Urology, Graduate School of Medicine, Yamaguchi University), Takahiro Kojima (Department of Urology, Faculty of Medicine, University of Tsukuba), Yasutomo Nasu (Department of Urology, Okayama University Graduate School of Medicine, Dentistry and Pharmaceutical Sciences), Motohide Uemura (Department of Urology, Osaka University Graduate School of Medicine).

Funding

The study was supported by Bayer.

Author information

NM, GK, Hiroji U, Hirotsugu U, MN, SN, AM, HKi, and YK were involved in the collection and interpretation of data; NM and GK were involved in drafting the manuscript; MH and SK were involved in establishing the procedure of blinding compatible with local regulations for radionuclide use; JS was accountable for planning the study, and analysis and interpretation of data; HKr was accountable for planning and involved in leading the study and interpretation of data; all authors reviewed the manuscript and approved the final version.

Correspondence to Nobuaki Matsubara.

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Conflict of interest

The authors disclose the following conflicts of interest: Nobuaki Matsubara has received research funding from Bayer. Go Kimura has received honoraria from Bayer. Hiroji Uemura has received research funding from Astellas, honoraria from Bayer, Janssen, Astellas, Takeda and Astra Zeneca, and received travel expenses from Janssen, Bayer, Astellas, Takeda and Astra Zeneca. Hirotsugu Uemura has received research funding from Astra Zeneca, Sanofi, Janssen, Takeda and Astellas, honoraria from Bayer, Astra Zeneca, Takeda, Sanofi, Janssen and Astellas, and has acted as an advisor to Sanofi, Janssen, and Bayer. Atsushi Mizokami has received honoraria from Bayer. Seigo Kinuya has received honoraria from Bayer. Heiko Krissel and Jonathan Siegel own stocks of Bayer AG, and are employees of Bayer AG and Bayer HealthCare Pharmaceuticals, respectively. All remaining authors declare no conflict of interest.

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Matsubara, N., Kimura, G., Uemura, H. et al. A randomized, double-blind, comparison of radium-223 and placebo, in combination with abiraterone acetate and prednisolone, in castration-resistant metastatic prostate cancer: subgroup analysis of Japanese patients in the ERA 223 study. Int J Clin Oncol (2019) doi:10.1007/s10147-019-01589-6

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Keywords

  • Abiraterone acetate
  • Castration-resistant prostate cancer
  • Fractures
  • Japanese patients
  • Radium-223
  • Symptomatic skeletal event