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Introduction: Radium-223, abiraterone, and enzalutamide have each been shown to significantly improve survival as monotherapy in patients with metastatic castration-resistant prostate cancer. However, effects of combination radium-223 plus abiraterone or enzalutamide on survival and safety remain unclear. Patients and methods: This single-center retrospective cohort study used electronic health record data of patients with metastatic castration-resistant prostate cancer and bone metastases who were treated with radium-223 between April 1, 2014 and February 19, 2019. Patients who received radium-223 monotherapy were compared to patients who received a combination of radium-223 plus either abiraterone or enzalutamide. The primary endpoint was overall survival. Secondary endpoints included progression-free survival, time to symptomatic skeletal event, symptomatic skeletal event-free survival, and incidence of drug-related adverse events. Time-to-event analyses were estimated by log rank tests using Kaplan-Meier curves. Hazard ratios and 95% confidence intervals were derived from Cox proportional hazards models. Chi-square tests evaluated difference in serious adverse events between the two arms. Results: A total of 60 patients met inclusion criteria (n = 41 in the monotherapy arm, n = 19 in the combination arm). Differences in median overall survival were not observed (12.7 vs. 12.8 months; HR 1.15, 95% CI 0.59–2.23; P = 0.68), but median progression-free survival was significantly longer in the combination arm (7.6 vs. 4.9 months; HR 1.94, 95% CI 1.11–3.40; P = 0.02). Significant differences were not observed in time to first SSE (P = 0.97), SSE-free survival (P = 0.16), or in the overall incidence of serious adverse events (P = 0.45). Conclusion: Combination radium-223 plus abiraterone or enzalutamide did not improve overall survival, but prolonged progression-free survival without increasing the incidence of serious adverse events in metastatic castration-resistant prostate cancer patients with bone metastases. However, these results are limited by small numbers and patient selection inherent in retrospective analysis. [ABSTRACT FROM AUTHOR]

B Writing-review & editing: b Stephanie I. Kim, Andy H. Szeto, Katherine P. Morgan, Blaine Brower, Mary W. Dunn, Amir H. Khandani, Tracy L. Rose, Ethan M. Basch, Matthew I. Milowsky, Young E. Whang, Daniel J. Crona. The following information is missing from the Funding statement: The authors would also like to gratefully acknowledge support provided by the Willis H. Thompson Prostate Cancer Research Fund. B Writing-original draft: b Stephanie I. Kim, Andy H. Szeto, Katherine P. Morgan, Blaine Brower, Mary W. Dunn, Amir H. Khandani, Tracy L. Rose, Ethan M. Basch, Matthew I. Milowsky, Young E. Whang, Daniel J. Crona. [Extracted from the article]