Nobuaki Matsubara1, Go Kimura2, Hiroji Uemura3, Hirotsugu Uemura4, Motonobu Nakamura5, Satoshi Nagamori6, Atsushi Mizokami7, Hiroaki Kikukawa8, Makoto Hosono9, Seigo Kinuya9, Heiko Krissel10, Jonathan Siegel11, Yoshiyuki Kakehi12. 1. Division of Breast and Medical Oncology, National Cancer Center Hospital East, 6-5-1 Kashiwanoha, Kashiwa, Chiba, 277-8577, Japan. nmatsuba@east.ncc.go.jp. 2. Department of Urology, Nippon Medical School, 1-1-5, Sendagi, Bunkyo-ku, Tokyo, Japan. 3. Department of Urology and Renal Transplantation, Yokohama City University Medical Center, 4-57, Urafune-cho, Minami-ku, Yokohama, Japan. 4. Department of Urology, Kindai University Faculty of Medicine, 377-2, Ohno-Higashi, Osaka-Sayama, Osaka, Japan. 5. Department of Urology, National Hospital Organization Kyushu Cancer Center, Fukuoka, 811-1395, Japan. 6. Department of Urology, National Hospital Organization Hokkaido Cancer Center, 2-3-54 Kikusui 4 Jo, Shiroishi-ku, Sapporo, Japan. 7. Department of Integrative Cancer Therapy and Urology, Kanazawa University Graduate School of Medical Science, 13-1 Takaramachi, Kanazawa, Ishikawa, Japan. 8. Department of Urology, National Hospital Organization Kumamoto Medical Center, 1-5 Ninomaru, Chuo-ku, Kumamoto, Japan. 9. The Japanese Society of Nuclear Medicine, 2-28-45, Honkomagome, Bunkyo-ku, Tokyo, Japan. 10. Clinical Development, SBU Oncology, Bayer AG, Berlin, Germany. 11. Clinical Statistics, Bayer HealthCare Pharmaceuticals, Whippany, NJ, USA. 12. Kagawa University, Takamatsu, Kagawa, Japan.
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.
RCT Entities:
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.
Authors: Oliver Sartor; Nicholas J Vogelzang; Christopher Sweeney; Daniel C Fernandez; Fabio Almeida; Andrei Iagaru; Alan Brown; Matthew R Smith; Manish Agrawal; Adam P Dicker; Jorge A Garcia; Jose Lutzky; Yu-Ning Wong; Oana Petrenciuc; Jeremy Gratt; Neal D Shore; Michael J Morris Journal: Oncologist Date: 2017-11-28
Authors: Matthew Smith; Chris Parker; Fred Saad; Kurt Miller; Bertrand Tombal; Quan Sing Ng; Martin Boegemann; Vsevolod Matveev; Josep Maria Piulats; Luis Eduardo Zucca; Oleg Karyakin; Go Kimura; Nobuaki Matsubara; William Carlos Nahas; Franco Nolè; Eli Rosenbaum; Axel Heidenreich; Yoshiyuki Kakehi; Amily Zhang; Heiko Krissel; Michael Teufel; Junwu Shen; Volker Wagner; Celestia Higano Journal: Lancet Oncol Date: 2019-02-06 Impact factor: 41.316
Authors: Mari I Suominen; Katja M Fagerlund; Jukka P Rissanen; Yvonne M Konkol; Jukka P Morko; ZhiQi Peng; Esa J Alhoniemi; Salla K Laine; Eva Corey; Dominik Mumberg; Karl Ziegelbauer; Sanna-Maria Käkönen; Jussi M Halleen; Robert L Vessella; Arne Scholz Journal: Clin Cancer Res Date: 2017-03-31 Impact factor: 12.531
Authors: Christopher C Parker; Robert E Coleman; Oliver Sartor; Nicholas J Vogelzang; David Bottomley; Daniel Heinrich; Svein I Helle; Joe M O'Sullivan; Sophie D Fosså; Aleš Chodacki; Paweł Wiechno; John Logue; Mihalj Seke; Anders Widmark; Dag Clement Johannessen; Peter Hoskin; Nicholas D James; Arne Solberg; Isabel Syndikus; Jan Kliment; Steffen Wedel; Sibylle Boehmer; Marcos Dall'Oglio; Lars Franzén; Øyvind S Bruland; Oana Petrenciuc; Karin Staudacher; Rui Li; Sten Nilsson Journal: Eur Urol Date: 2017-07-11 Impact factor: 20.096
Authors: William T Lowrance; Mohammad Hassan Murad; William K Oh; David F Jarrard; Matthew J Resnick; Michael S Cookson Journal: J Urol Date: 2018-08-04 Impact factor: 7.450
Authors: Howard I Scher; Susan Halabi; Ian Tannock; Michael Morris; Cora N Sternberg; Michael A Carducci; Mario A Eisenberger; Celestia Higano; Glenn J Bubley; Robert Dreicer; Daniel Petrylak; Philip Kantoff; Ethan Basch; William Kevin Kelly; William D Figg; Eric J Small; Tomasz M Beer; George Wilding; Alison Martin; Maha Hussain Journal: J Clin Oncol Date: 2008-03-01 Impact factor: 44.544
Authors: S Nilsson; P Cislo; O Sartor; N J Vogelzang; R E Coleman; J M O'Sullivan; J Reuning-Scherer; M Shan; L Zhan; C Parker Journal: Ann Oncol Date: 2016-02-23 Impact factor: 32.976