Concurrent or layered treatment with radium-223 and enzalutamide or abiraterone/prednisone: real-world clinical outcomes in patients with metastatic castration-resistant prostate cancer

Prostate Cancer Prostatic Dis. 2020 Dec;23(4):680-688. doi: 10.1038/s41391-020-0236-0. Epub 2020 May 13.

Abstract

Background: In this study, we evaluated real-world data on radium-223 plus abiraterone/prednisone or enzalutamide. Previously, the ERA 223 trial (NCT02043678) demonstrated increased fracture risk with concurrent treatment with radium-223 and abiraterone plus prednisone/prednisolone in patients with metastatic castration-resistant prostate cancer (mCRPC).

Methods: We used the Flatiron Health database to perform a retrospective study of patients with mCRPC treated with radium-223. Treatment with radium-223 plus abiraterone/prednisone or enzalutamide was defined as concurrent if both drugs started within 30 days of one another, or layered when the second drug started ≥30 days after the first. The index date was defined as the day of the first radium-223 dose. Outcome measures included symptomatic skeletal events (SSEs), overall survival (OS), and patterns of treatments received.

Results: Of the 625 patients treated with radium-223, 22% received it together with abiraterone/prednisone and 27% with enzalutamide. When these agents were combined, they were often initiated in a layered fashion (73% layered, 23% concurrent). Prior or concomitant bone health agents (BHAs) were received by 67% and 55% of patients, respectively. Median follow-up was 9 months. Overall, incidence rates for SSEs and pathologic fractures were 0.35 and 0.11 patients per person-year, respectively. Median OS from mCRPC diagnosis was 28.1 months.

Conclusions: In this real-world setting, combination treatments with radium-223 and abiraterone/prednisone or enzalutamide were common. These agents were more commonly given in a layered than a concurrent fashion. Incidence rates for SSEs were reduced when BHAs were used; however, BHAs were underutilized.

Publication types

  • Research Support, Non-U.S. Gov't

MeSH terms

  • Adult
  • Aged
  • Aged, 80 and over
  • Androstenes / administration & dosage
  • Antineoplastic Combined Chemotherapy Protocols / therapeutic use*
  • Benzamides / administration & dosage
  • Bone Density Conservation Agents / therapeutic use*
  • Bone Neoplasms / drug therapy*
  • Bone Neoplasms / secondary
  • Chemoradiotherapy
  • Clinical Trials, Phase III as Topic
  • Denosumab / therapeutic use
  • Humans
  • Male
  • Middle Aged
  • Multicenter Studies as Topic
  • Neoplasm Metastasis
  • Nitriles / administration & dosage
  • Phenylthiohydantoin / administration & dosage
  • Prednisone / administration & dosage
  • Prostatic Neoplasms, Castration-Resistant / drug therapy*
  • Prostatic Neoplasms, Castration-Resistant / pathology
  • Radium / therapeutic use*
  • Randomized Controlled Trials as Topic
  • Retrospective Studies
  • Survival Rate
  • Treatment Outcome
  • Zoledronic Acid / therapeutic use

Substances

  • Androstenes
  • Benzamides
  • Bone Density Conservation Agents
  • Nitriles
  • Phenylthiohydantoin
  • Denosumab
  • Zoledronic Acid
  • Radium-223
  • enzalutamide
  • abiraterone
  • Prednisone
  • Radium

Associated data

  • ClinicalTrials.gov/NCT02043678