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. 2020 Apr;25(4):720-731. doi: 10.1007/s10147-019-01589-6. Epub 2019 Dec 10.

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.

Keywords: Abiraterone acetate; Castration-resistant prostate cancer; Fractures; Japanese patients; Radium-223; Symptomatic skeletal event.

Publication types

  • Randomized Controlled Trial

MeSH terms

  • Abiraterone Acetate / administration & dosage
  • Aged
  • Aged, 80 and over
  • Antineoplastic Combined Chemotherapy Protocols / adverse effects
  • Antineoplastic Combined Chemotherapy Protocols / therapeutic use*
  • Asian People
  • Bone Neoplasms / secondary
  • Disease-Free Survival
  • Double-Blind Method
  • Fractures, Bone / chemically induced
  • Humans
  • Male
  • Middle Aged
  • Placebos
  • Prednisolone / administration & dosage
  • Prednisone / administration & dosage
  • Prostatic Neoplasms, Castration-Resistant / drug therapy*
  • Prostatic Neoplasms, Castration-Resistant / mortality*
  • Prostatic Neoplasms, Castration-Resistant / pathology
  • Radium / administration & dosage
  • Treatment Outcome

Substances

  • Placebos
  • Radium-223
  • Prednisolone
  • Abiraterone Acetate
  • Prednisone
  • Radium

Associated data

  • ClinicalTrials.gov/NCT02043678