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Final overall survival results from the phase 3 EORTC 1333/PEACE-3 trial, presented at the 2026 ASCO Genitourinary Cancers Symposium and published simultaneously in the Annals of Oncology, showed that the combination of radium-223 (Xofigo) and enzalutamide (Xtandi) reduced the risk of death by 24% compared with enzalutamide alone in men with metastatic castration-resistant prostate cancer and bone metastases.
Lead author Enrique Gallardo, MD, of Parc Tauli Hospital Universitari in Sabadell, Spain, reported a median overall survival of 38.2 months with the combination versus 32.6 months with enzalutamide alone (HR 0.76; 95% CI, 0.60-0.96; P=.0096). The 446 enrolled patients were asymptomatic or mildly symptomatic and had received no prior androgen receptor pathway inhibitor therapy. Patients received enzalutamide continuously while the combination arm received six intravenous injections of radium-223.
Discussant Evan Yu, MD, of the Fred Hutchinson Cancer Center, described a statistically significant overall survival benefit as notable in a disease setting where achieving this endpoint has grown increasingly difficult given the number of active agents already available.
The trial authors recommended co-administration of a bone-protecting agent to reduce skeletal complications, a consideration that managed care organizations will need to build into clinical policy. Radium-223 is a less costly option than newer radioligand therapies such as lutetium-177 PSMA, and the PEACE-3 findings may prompt interest in sequencing strategies.
For frontline care teams and payers, the practical questions center on patient selection, prior ARPI exposure, and how the combination fits within current formularies, given that XOFIGO is not currently approved for this specific investigational indication in combination with enzalutamide. Updated safety data showed no new signals beyond the known profiles of each agent.
