Safety of concomitant therapy with radium-223 and abiraterone or enzalutamide in a real-world population

Hanson Zhao, Lauren E. Howard, Amanda M. De Hoedt, Martha K. Terris, Christopher L. Amling, Christopher J. Kane, Matthew R. Cooperberg, William J. Aronson, Zachary Klaassen, Thomas J. Polascik, Adriana C. Vidal, Stephen J. Freedland

Research output: Contribution to journalArticlepeer-review

6 Scopus citations


Background: Real-world utilization and outcomes of combination therapy for men with metastatic castrate-resistant prostate cancer (mCRPC) are largely unknown. We evaluated the overall survival (OS) and skeletal-related events (SREs) among men who received radium-223 with or without concomitant abiraterone or enzalutamide in the Veterans Affairs (VA) Health System. Methods: We reviewed charts of all mCRPC patients who received radium-223 in the VA from January 2013 to September 2017. We used Cox models to test the association between concomitant therapy versus radium-223 alone on OS and SRE. Sensitivity analyses were performed for concomitant use of denosumab/bisphosphonates. Results: Three hundred and eighteen patients treated with radium-223 were identified; 116/318 (37%) received concomitant abiraterone/enzalutamide. Two hundred and seventy-seven (87%) patients died during follow-up. Patients who received concomitant therapy were younger at radium-223 initiation (median age 68 vs. 70, p =.027) and had a longer follow-up (median 29.5 vs. 17.9 months, p =.030). There was no OS benefit for those on concomitant therapy (hazard ratio [HR]: 0.87, 95% confidence interval [CI]: 0.67–1.12, p =.28). There was a trend for an increased SRE risk for patients on concomitant therapy (HR: 1.87, 95% CI: 0.96–3.61, p =.066), but this was not significant. When analyses were limited to men using bone heath agents, similar results were seen for OS (HR: 0.86, 95% CI 0.64–1.15, p =.30) and SRE (HR: 2.36, 95% CI: 0.94–5.94, p =.068). Conclusions: Despite the common use of concomitant therapy in this real-world study, there was no difference in OS among mCRPC patients. A nonsignificant increased SRE risk was observed. Further work needs to evaluate the optimal sequence, timing, and safety of combination therapies.

Original languageEnglish (US)
Pages (from-to)390-397
Number of pages8
Issue number7
StatePublished - May 15 2021


  • abiraterone
  • concomitant therapy
  • enzalutamide
  • metastatic prostate cancer
  • radium-223

ASJC Scopus subject areas

  • Oncology
  • Urology


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