Final overall survival results from EORTC 1333/PEACE-3 trial of enzalutamide plus radium-223 in metastatic castration-resistant prostate cancer
Mené sur 446 patients atteints d'un cancer de la prostate résistant à la castration et de stade métastatique (durée médiane de suivi : 58 mois), cet essai de phase III évalue l'efficacité, du point de vue de la survie globale, et la toxicité de l'ajout de radium-223 à l'enzalutamide en traitement de première ligne
Background: The primary analysis of the EORTC 1333/PEACE-3 study demonstrated that enzalutamide plus radium-223 (Ra223) improved radiological progression-free survival (rPFS) compared to enzalutamide alone in patients with metastatic castration-resistant prostate cancer (mCRPC). The primary endpoint was rPFS while overall survival (OS) was a key secondary endpoint. Interim overall survival (OS) results were reported at time of primary analysis. Here, we report the final overall survival (OS) analysis.
Patients and methods: From November 2015 to March 2023, 446 patients were randomised to receive enzalutamide alone or enzalutamide combined with six cycles of Ra223. Co-administration of bone-protecting agents (BPA) became mandatory for all patients from March 2018. Final analysis of OS was triggered on 1 May 2025.
Results: With a median follow-up of 58 months and 317 reported deaths, the hazard ratio (HR) was 0.76 [95% CI 0.60-0.96, p=0.0096] for OS in favour of the enzalutamide + Ra223 arm reaching the predefined level of statistical significance of <0.0248. Median OS was 32.6 months (95%CI 29.3-38.2) in the enzalutamide arm (n=224) and 38.2 months (95%CI 33.1-44.8) in the combination arm (n=222). The HR for rPFS was 0.71 (95% 0.57-0.89). Treatment-emergent grade
≥
3 adverse events increased from 57.6% to 69.3% in the combination arm, as did treatment-related grade
≥
3 TEAEs (18.8% vs 28.9%), the most frequent being hypertension.
Conclusion: The final analysis of this study confirmed that the combination of enzalutamide with Ra223 significantly improved not only rPFS but also OS as first-line therapy for mCRPC versus enzalutamide alone. Co-administration of a bone-protecting agent is required to reduce skeletal complications.
Annals of Oncology , article en libre accès, 2026