Dr Qin on Ongoing Investigations of Radium-223 in mCRPC

"Treatment selection is still a clinical question based on [factors such as] patient characteristics, comorbidities, etc. I'm not sure they’ll truly help answer the sequencing question at this time, but [there are ongoing trials] looking at different combinations with radium-223."

Qian (Janie) Qin, MD, an assistant professor in the Department of Internal Medicine at UT Southwestern Medical Center and the Eugene P. Frenkel, MD Scholar in Clinical Medicine at Harold C. Simmons Comprehensive Cancer Center, discussed ongoing trials aiming to clarify the optimal role of radium 223 (Xofigo) plus enzalutamide (Xtandi) in metastatic castration-resistant prostate cancer (mCRPC), as well as the importance of patient factors when considering the selection of this regimen.

Findings from the phase 3 PEACE-3 trial (NCT02194842), recently published in Annals of Oncology in May 2025 following prior presentation at the 2024 ESMO Congress, demonstrated a significant radiographic progression-free survival (rPFS) benefit with the addition of radium-223 to enzalutamide. Specifically, the combination reduced the risk of radiographic progression or death by 31% compared with enzalutamide alone (HR, 0.69; 95% CI, 0.54-0.87; P = .0009).

Although the combination appears clinically and statistically beneficial, patient selection remains key, Qin emphasized. In her practice, radium-223 may be considered for patients with bone-predominant metastases who are asymptomatic or minimally symptomatic, are not candidates for chemotherapy, and have a slower prostate-specific antigen (PSA) rise. In such cases, especially where an alternative androgen receptor pathway inhibitor switch is also under consideration, radium-223 in combination with enzalutamide could be a reasonable approach supported by PEACE-3 data.

Several trials are exploring new radium-223 combinations, although they may not fully address optimal sequencing strategies, Qin continued. The ongoing phase 3 DORA trial (NCT03574571) is evaluating radium-223 in combination with docetaxel compared with docetaxel alone in mCRPC, which may inform the use of radium-223 in chemotherapy-eligible patients. Additionally, the phase 1/2 AlphaBet trial (NCT05383079) is investigating the combination of radium-223 with 177Lu-PSMA-I&T, a radioligand therapy targeting PSMA. These trials may help refine how radium-223 fits into evolving mCRPC treatment paradigms, though definitive sequencing guidance remains a future goal, Qin concluded.