Final overall survival results from the EORTC 1333/PEACE-3 trial: Enzalutamide with or without radium-223 in metastatic castration-resistant prostate cancer.

Abstract

15 Background: In EORTC1333.PEACE-3 the combination of enzalutamide and radium-223 (ENZ/RAD) prolonged rPFS and OS (interim analysis) in patients with mCRPC with bone metastases, with a safety similar to that of each treatment alone, versus enzalutamide alone (ENZ). Here we report the final OS analysis an updated safety data. Methods: EORTC1333/PEACE-3 is a randomized, open-label, multicentre phase III trial evaluating the addition of radium-223 (ENZ/RAD) to enzalutamide (ENZ) in metastatic castration-resistant prostate cancer (mCRPC) with bone metastases. In PEACE-3, a total of 446 asymptomatic or mildly symptomatic patients (Brief Pain Inventory <4) with mCRPC and ≥2 bone metastases were randomized 1:1 to Enza 160 mg daily alone or combined with six intravenous injections of Ra-223 (55 kBq/kg every 4 weeks). The study was conducted in collaboration with Clinical Trial Ireland (CTI), the Canadian Urological Oncology Group (CUOG), the Latin American Cooperative Oncology Group (LACOG), and the French group GETUG/UNICANCER. The primary endpoint was radiological progression-free survival (rPFS); overall survival (OS) and safety were key secondary endpoint. Results: At the final database lock (19 September 2025), 318 deaths were recorded (152/222 Enza+Ra-223; 166/224 Enza), representing 106.4% of the 299 expected events. Median OS was 38.2 months for Enza+Ra-223 and 32.6 months for Enza alone, corresponding to a hazard ratio (HR) of 0.75 (95% CI 0.60–0.95; one-sided stratified logrank p-value=0.0078, with a preset level of significance at final analysis of <0.0248.. Based on the permutation test, the statistical test on OS is significant (resulting in a 1-sided p-value of 0.0088 < 0.0248). The OS benefit was consistent across most predefined subgroups, except for age >75, for which the interaction was significant at the 10% 2-sided level. The previously published primary analysis (Ann Oncol 2025) demonstrated a significant improvement in rPFS (19.4 vs 16.4 months; HR 0.69; 95% CI 0.54–0.87; p=0.0009). The final analysis consolidates these findings, confirming prolonged OS and no new safety signals. Conclusions: The final results of EORTC1333/PEACE-3 confirm that adding six cycles of radium-223 to enzalutamide significantly prolongs overall survival in men with bone-dominant mCRPC, supporting the synergistic potential of this combination. Detailed analyses of efficacy, safety, and subgroups will be presented. Clinical trial information: NCT02194842 .