ASCO GU 2020: Safety and Effectiveness of Radium-223 Dichloride in Patients with mCRPC in Real-World Setting: A Japanese Post-Marketing Study

San Francisco, California ( Radium-223 is the first targeted alpha therapy approved for castration-resistant prostate cancer (CRPC) with symptomatic bone metastases. In Japan, Radium-223 was approved as a treatment for CRPC with bone metastasis in March 2016 based on the results of the Phase III ALSYMPCA study1 and the Japanese phase II study.2 Japanese post-marketing surveillance has been conducted since the launch of Radium-223 in accordance with Japanese authorities. Due to the limitations of a clinical study such as short observation periods and selected patient populations, it is necessary to grasp the safety and effectiveness of a newly approved drug in the clinical setting. Presenting during the Prostate Cancer Session at the 2020 American Society of Clinical Oncology Genitourinary Cancers Symposium (ASCO GU), Dr. Takahashi and colleagues shared results of their post-marketing surveillance data for the use of Radium-223 in Japan.

This study was a prospective, single-arm, observational study of patients with metastatic castration-resistant prostate cancer (mCRPC) treated with up to six cycles of Radium-223 and a planned sample size of 300. In this primary analysis, clinical outcomes during the 6-month observational period up to one month after the last injection of Radium-223 were assessed. An exploratory subgroup analysis was performed according to symptom status at baseline.

There were 334 patients enrolled from June 2016 to November 2017. As of November 2019, data for 296 patients were available. The median observational period was 5.6 months (range 1.0-10.6). Among the 296 patients, 70.6% had previously received abiraterone and/or enzalutamide, and 40.5% of patients had been previously treated with docetaxel. There were 203 patients that made up the asymptomatic group and 93 patients that made up the symptomatic group. The incidence of drug-related any treatment-emergent adverse events was 27%, hematologic treatment-emergent adverse events was 18%, and skeletal-related events were 3%. Fractures were reported in 5 patients, but all were judged not related to Radium-223 by investigators. For the subgroup analysis, baseline characteristics for asymptomatic-group seemed more favorable than those in symptomatic-group. More patients in asymptomatic-group completed six cycles of Radium-223, and incidence of drug-related treatment-emergent adverse events appeared lower in the asymptomatic-group compared with the symptomatic-group.

As follows are the changes in PSA by symptom group:

changes in PSA by symptom group

And by the number of injections received:

number of injections received

Dr. Takahashi concluded this real-world experience with Radium-223 in Japan presentation with the following summary points:

  • This is the first report of real-world data of 296 Japanese patients with mCRPC treated with Radium-223
  • In this Japanese cohort, most of the patients (~70%) had a performance status of 0 and were asymptomatic
  • During the six-month observational period, no new safety concerns related to Radium-223 were reported
  • Asymptomatic patients were more likely to complete six cycles of Radium-223 treatment and experience fewer treatment-emergent adverse events compared to symptomatic patients, possibly reflecting less advanced disease and less use of prior chemotherapy and/or abiraterone/enzalutamide
  • The number of patients who experienced fractures during the six-month observational period was small
  • A 3-year follow-up observation is ongoing
Presented by: Shunji Takahashi, Md, Deputy Director, Cancer Institute Hospital, Department Director, Medical Oncology, The Cancer Institute Hospital of the Japanese Foundation for Cancer Research, Tokyo, Japan

Co-Authors: Yoshiyuki Kakehi, Naoya Masumori, Makoto Hosono, Seigo Kinuya, Yutaka Okayama, Toshiyuki Sunaya, Masafumi Okumura, Hirotsugu Uemura; Cancer Institute Hospital of the Japanese Foundation for Cancer Research, Tokyo, Japan; Kagawa University, Kagawa, Japan; Department of Urology, School of Medicine, Sapporo Medical University, Hokkaido, Japan; Department of Radiology, Kindai University Faculty of Medicine, Osaka-Sayama, Japan; Department of Nuclear Medicine, Kanazawa University Hospital, Kanazawa, Japan; Bayer Yakuhin, Ltd, Osaka, Japan; Bayer Yakuhin, Ltd., Osaka, Japan; Department of Urology, Kindai University Faculty of Medicine, Osaka, Japan

Written by: Zachary Klaassen, MD, MSc, Assistant Professor of Urology, Georgia Cancer Center, Augusta University/Medical College of Georgia, Twitter: @zklaassen_md at the 2020 Genitourinary Cancers Symposium, ASCO GU #GU20, February 13-15, 2020, San Francisco, California 


1. Parker, Christopher, S. Nilsson, Daniel Heinrich, Svein I. Helle, J. M. O'sullivan, Sophie D. Foss√•, AleŇ° Chodacki et al. "Alpha emitter radium-223 and survival in metastatic prostate cancer." New England Journal of Medicine 369, no. 3 (2013): 213-223.

2. Matsubara, Nobuaki, Satsohi Nagamori, Yoshiaki Wakumoto, Hirotsugu Uemura, Go Kimura, Akira Yokomizo, Hiroaki Kikukawa et al. "Phase II study of radium-223 dichloride in Japanese patients with symptomatic castration-resistant prostate cancer." International journal of clinical oncology 23, no. 1 (2018): 173-180.
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