Dr Saad on the Efficacy and Safety of Radium-223 Plus Enzalutamide in mCRPC

"[We saw] that there's a 31% reduction in the risk of radiographic progression [with the addition of] radium-223 to enzalutamide over enzalutamide alone. This was very statistically, and in my opinion clinically, significant [in showing that] we can do better than an ARPI alone. These are good, reassuring data."

Fred Saad, CQ, MD, FRCS, FCAHS, director of Prostate Cancer Research at the Montreal Cancer Institute and a uro-oncologist at the University of Montreal Health Center, discussed the recent publication of data from the phase 3 PEACE-3 trial (NCT02194842), which evaluated the combination of radium-223 (Xofigo) and enzalutamide (Xtandi) in patients with metastatic castration-resistant prostate cancer (mCRPC) and predominant bone metastases.

As recently published in Annals of Oncology in May 2025, following prior presentation at the 2024 ESMO Congress, the trial met its primary endpoint, demonstrating a statistically and clinically significant improvement in radiographic progression-free survival (rPFS) with the addition of radium-223 to enzalutamide. Specifically, the combination reduced the risk of progression or death by 31% compared with enzalutamide alone (HR, 0.69; 95% CI, 0.54-0.87; P = .0009).

Saad emphasized that this finding supports a treatment strategy that goes beyond androgen receptor pathway inhibitor (ARPI) monotherapy. The combination was also associated with encouraging overall survival (OS) data, which continue to mature. Preliminary findings show a similar 31% reduction in the risk of death with the addition of radium-223, although final statistical significance for this endpoint is pending. Importantly, the safety profile of the combination was favorable, with few unexpected adverse effects observed, and most patients were able to complete the full 6 cycles of radium-223 when given early in their disease course.

Additionally, Saad highlighted updated data related to bone health agents (BHAs) from the trial. Long-term follow-up suggests that early initiation of BHAs was associated with improved rPFS and OS, reinforcing their role not only in delaying skeletal-related complications but potentially also in prolonging survival in this population.

These findings underscore the therapeutic value of combining radium-223 with enzalutamide and support the integration of BHAs early in the treatment paradigm for patients with mCRPC and bone-predominant disease.