Enzalutamide plus radium-223 in metastatic castration-resistant prostate cancer : results of the EORTC 1333/PEACE-3 trial
Tombal, B. (Cliniques Universitaires Saint Luc)
Choudhury, Ananyo (The Christie NHS Foundation Trust (Manchester, Regne Unit))
Gallardo, Eduard (Parc Taulí Hospital Universitari. Institut d'Investigació i Innovació Parc Taulí (I3PT))
Soares, A. (Hospital Israelita Albert Einstein (Sao Paolo, Brasil))
Loriot, Yohann (Université Paris-Saclay)
McDermott, R. (Tallaght University Hospital)
Silva Melo Cruz, Felipe José (Instituto Brasileiro de Controle do Câncer)
Roumeguere, T. (HUB. Hôpital Erasme)
Bompas, E. (Institut de Cancérologie de l'Ouest (France))
Gomez Veiga, F. (Complejo Hospitalario Universitario de A Coruña)
Martins da Trindade, K. (Instituto D'Or de Pesquisa e Ensino)
Lecouvet, F. (Cliniques Universitaires Saint Luc)
Saad, F. (Centre Hospitalier de l'Université de Montréal)
Rodriguez-Vida, A. (Hospital del Mar (Barcelona, Catalunya))
Isaacsson Velho, P. (Moinhos de Vento Hospital)
Nolè, F. (IEO. Istituto Europeo di Oncologia IRCCS)
Daugaard, G. (University of Copenhagen)
Yamamura, R. (Beneficência Portuguesa de São Paulo)
Maroto Rey, Pablo (Institut de Recerca Sant Pau)
Skoneczna, I. (Maria Sklodowska Curie Memorial Cancer Centre)
Mavignier Carcano, F. (Hospital de Câncer de Barretos)
Coens, C. (European Organisation of Research and Treatment of Cancer (Brussels, Bèlgica))
Poncet, C. (European Organisation of Research and Treatment of Cancer (Brussels, Bèlgica))
Fournier, B. (European Organisation of Research and Treatment of Cancer (Brussels, Bèlgica))
Gillessen, S. (Università della Svizzera Italiana. Faculty of Biosciences)
Universitat Autònoma de Barcelona. Departament de Medicina

Date:	2025
Abstract:	Background: The EORTC 1333 'PEACE-3' study investigated the combination of enzalutamide and 6 monthly injections of radium-223 (Ra223) in patients with metastatic castration-resistant prostate cancer (mCRPC) and bone metastases. Materials and methods: From November 2015 to March 2023, 446 patients, including 11 who received abiraterone, were randomized to enzalutamide (without placebo) or enzalutamide combined with six cycles of Ra223. As of March 2018, the co-administration of zoledronic acid or denosumab was mandatory. The primary endpoint was radiological progression-free survival (rPFS) by investigator assessment. Key secondary endpoints included overall survival (OS), time to subsequent systemic treatment, pain progression, and symptomatic skeletal event. Results: The hazard ratio (HR) for rPFS was 0. 69 [95% confidence interval (CI) 0. 54-0. 87, P = 0. 0009], with a median rPFS of 16. 4 months (95% CI 13. 8-19. 2 months) in the enzalutamide arm and 19. 4 months (95% CI 17. 1-25. 3 months) in the combination arm. At the preplanned interim analysis conducted at 80% of the OS events, the HR for OS was 0. 69 (95% CI 0. 52-0. 90, P = 0. 0031), with a median OS of 35. 0 months (95% CI 28. 8-38. 9 months) in the enzalutamide arm and 42. 3 months (95% CI 36. 8-49. 1 months) in the combination arm. Due to non-proportional hazards, this will be tested further at the final OS analysis. Treatment-emergent adverse events (TEAEs) ≥ grade 3 were recorded in 55. 8% and 65. 6% of the patients in the enzalutamide and combination arms, respectively. The most frequent grade ≥3 TEAEs in the combination arm were hypertension (34%), fatigue (6%), fracture (5%), anemia (5%), and neutropenia (5%). Fractures [either treatment-emergent or post-treatment, symptomatic or pathologic, or with or without bone-protecting agent (BPA) use] were reported in 30 (13. 4%) patients in the enzalutamide arm and 53 patients (24. 3%) in the combination arm. Conclusion: PEACE-3 demonstrates that combining enzalutamide with Ra223 as first-line therapy for mCRPC significantly improves rPFS. Although statistically significant at the OS interim boundary, the study will continue to the final OS analysis.
Rights:	Aquest document està subjecte a una llicència d'ús Creative Commons. Es permet la reproducció total o parcial, la distribució, la comunicació pública de l'obra i la creació d'obres derivades, fins i tot amb finalitats comercials, sempre i quan es reconegui l'autoria de l'obra original.
Language:	Anglès
Document:	Article ; recerca ; Versió publicada
Subject:	bone metastases ; enzalutamide ; metastatic castration-resistant prostate cancer ; radium-223
Published in:	Annals of oncology, Vol. 36, Num. 9 (September 2025) , p. 1058-1067, ISSN 1569-8041

DOI: 10.1016/j.annonc.2025.05.011
PMID: 40450503

10 p, 428.4 KB

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Research literature > UAB research groups literature > Research Centres and Groups (research output) > Health sciences and biosciences > Parc Taulí Research and Innovation Institute (I3PT
Research literature > UAB research groups literature > Research Centres and Groups (research output) > Health sciences and biosciences > Institut de Recerca Sant Pau
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