According to results from a randomized, double-blind, placebo-controlled, multicenter, phase 3 trial abiraterone acetate plus prednisone or prednisolone in combination with radium-223, an alpha-particle emitting isotope of radium, was associated with an increased risk of bone fractures compared with placebo. This study was published online in Lancet Oncology.1
Both radium-223 and abiraterone acetate are approved by the United States Food and Drug Administration (FDA), the latter drug in combination with prednisone or prednisolone, for the treatment of patients with metastatic castration-resistant prostate cancer. 2,3 Radium-223, which has been shown to form complexes with bone metastases, is specifically indicated for patients with symptomatic bone metastases without evidence of visceral disease.3 This approval was based on results of a the ALSYMPCA trial, which showed increased overall survival (OS), delayed onset of symptomatic skeletal events, and fewer treatment-emergent adverse events for those who were administered radium-223 compared with those who received placebo.3 These results provided the rationale for investigating radium-223 in combination with other agents used in the treatment of castration-resistant prostate cancer, such as abiraterone acetate, an androgen biosynthesis blocker, which may have mechanisms of action that are complementary to radium-223.
In the current study, 806 patients with castration-resistant prostate cancer with asymptomatic or mildly symptomatic bone metastases were randomly assigned (1:1) to receive abiraterone plus prednisone/prednisolone in combination with radium-223 or placebo. The primary end point of the study was symptomatic skeletal event-free survival; secondary end points included OS, time to cytotoxic chemotherapy, radiological progression-free survival, time to pain, and safety.
Median symptomatic skeletal event-free survival was 22.3 months in the group receiving radium-223 and 26.0 months in the group receiving placebo (hazard ratio [HR]=1.122; 95% confidence interval [CI], 0.917-1.374; P =0.2636). Treatment-emergent bone fractures occurred in 26% and 10% of the patients receiving radium-223 and placebo, respectively. Grade 3/4 treatment-emergent bone fractures occurred in 9% in the radium-223 group compared with 3% in the group receiving placebo. The difference in OS between the 2 study arms (30.7 months [radium-223]; 33.3 months [placebo]) was not significant (P =0.1280).
In their concluding statements, the authors wrote, “We do not recommend use of radium-223 in combination with abiraterone acetate plus prednisone or prednisolone.”
- Smith M, Parker C, Saad F, et al. Addition of radium-223 to abiraterone acetate and prednisone or prednisolone in patients with castration-resistant prostate cancer and bone metastases (ERA 223): a randomised, double-blind, placebo-controlled, phase 3 trial [published online Febuary 6, 2019]. Lancet Oncol. doi: 10.1016/S1470-2045(18)30860-X
- Radium-223 (Xofigo) [package insert]. Wayne, NJ: Bayer Healthcare Pharmaceuticals, Inc. 2013.
- Abiraterone acetate (Zytiga) [package insert]. Horsham, PA: Janssen Pharmaceutical Companies. 2018.