Real‐World Outcomes of Combination Therapy With Radium‐223 and Enzalutamide Compared With Enzalutamide Alone in Patients With Metastatic Castration‐Resistant Prostate Cancer

Radium‐223 and enzalutamide have shown survival benefits in metastatic castration‐resistant prostate cancer, and recent trial data suggest a potential synergy in combination. However, real‐world data on their combined use, especially regarding fracture risk and prior androgen receptor signaling inhibitor exposure, are limited. In this study, we aimed to evaluate the efficacy and safety of adding radium‐223 to enzalutamide compared with enzalutamide alone in patients with bone metastatic castration‐resistant prostate cancer. We retrospectively included patients treated with radium‐223 plus enzalutamide (the combination group) or enzalutamide alone (the enzalutamide group), and compared progression‐free survival, overall survival, prostate‐specific antigen kinetics, alkaline phosphatase kinetics, and treatment‐emergent adverse events. A total of 17 and 18 patients were included in the combination and enzalutamide groups, and the median age and follow‐up duration were 75 years and 23 months, respectively. The median progression‐free survival was significantly longer in the combination group (22 months [95% confidence interval (CI): 16.7–32.4]) than that in the enzalutamide group (5 months [95% CI: 6.3–25.2], p = 0.048). However, there was no significant difference in overall survival (combination: not reached [95% CI: 31.1–44.8] vs. enzalutamide: not reached [95% CI: 28.9–56.5], p = 0.602). In the combination group, there was no significant difference in progression‐free and overall survival between patients with and without prior androgen receptor signaling inhibitor therapy. Fractures occurred in one (5.9%) and two (11.1%) patients in the combination and enzalutamide groups, respectively. In conclusion, the combination of radium‐223 and enzalutamide did not improve overall survival in patients with metastatic castration‐resistant prostate cancer. However, it significantly prolonged progression‐free survival without increasing the risk of fractures when bone health agents were administered. Furthermore, prior exposure to androgen receptor signaling inhibitors was not associated with oncological outcomes of the combination therapy.