Dr Saad on Long-Term Data With Radium-223 Plus Enzalutamide in mCRPC With Bone-Predominant Disease

“[The incidence of] secondary malignancies, which was one of the main issues, was only 2% so for this age group. It was very reassuring that we're not seeing an increased rate of secondary malignancies, which we might expect over time.”

Fred Saad, CQ, MD, FRCS, FCAHS, director of prostate cancer research at Montreal Cancer Institute, as well as a full professor in the Department of Surgery and a uro-oncologist in the Department of Urology at the University of Montreal Hospital Center, discussed safety and efficacy findings from the phase 3 PEACE-3 trial (NCT02194842), which evaluated the combination of radium-223 dichloride (Xofigo) and enzalutamide (Xtandi) in patients with metastatic castration-resistant prostate cancer (mCRPC) with bone-predominant disease.

The PEACE-3 study aimed to assess the safety of combining the alpha-emitting radiopharmaceutical radium-223 with an androgen receptor inhibitor, addressing prior concerns regarding potential long-term toxicities and skeletal complications.

Saad highlighted that the incidence of secondary malignancies among patients treated with the combination was low, occurring in only 2% of treated patients. This rate was consistent with the expected background risk for this patient population and age group, providing reassurance regarding the long-term safety of radium-223 exposure.

Fracture incidence was another key end point of the trial. The overall rate of fractures was 10%. Saad noted that this finding was clinically relevant given the bone-predominant disease burden and prolonged treatment exposure. Importantly, the study demonstrated a significant reduction in fracture risk among patients receiving concurrent bone health agents, such as bisphosphonates or denosumab (Xgeva). Patients on these agents typically experienced a fracture rate of approximately 7%, compared with approximately 12% among those not receiving bone-protective therapy—effectively a doubling of risk in the absence of such agents.

At a median follow-up of approximately 17 months, the median overall survival (OS) for patients treated with radium-223 in combination with enzalutamide was 15.6 months (95% CI, 14.6-16.4). Saad noted that this outcome compared favorably with historical data from the pivotal phase 3 ALSYMPCA trial (NCT00699751), suggesting durable efficacy and manageable toxicity with optimized supportive care.

Collectively, results from PEACE-3 support the continued use of radium-223 in combination regimens for appropriately selected patients with mCRPC and bone-predominant disease. The low incidence of secondary malignancies and the clear benefit of bone health agents underscore the evolving emphasis on survivorship and long-term safety in advanced prostate cancer management.