Final overall survival results from EORTC 1333/PEACE-3 trial of enzalutamide plus radium-223 in metastatic castration-resistant prostate cancer


Por: Gillessen, S, Gallardo, E, Choudhury, A, Saad, F, Soares, A, Loriot, Y, McDermott, R, Rodriguez-Vida, A, Velho, PI, Nolè, F, Cruz, F, Roumeguere, T, Daugaard, G, Yamamura, R, Bompas, E, Maroto, P, Veiga, FG, Skoneczna, I, da Trindade, KM, Carcano, FM, Lecouvet, F, Coens, C, Poncet, C, Fournier, B, Tombal, B

Publicada: 1 may 2026 Ahead of Print: 1 abr 2026
Resumen:
Background: The primary analysis of the European Organisation for Research and Treatment of Cancer (EORTC) 1333/PEACE-3 study demonstrated that enzalutamide plus radium-223 (Ra223) improved radiological progression-free survival (rPFS) compared with 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 OS results were reported at the time of primary analysis. Here, we report the final OS analysis. Patients and methods: From November 2015 to March 2023, 446 patients were randomly assigned to receive enzalutamide alone or enzalutamide combined with six cycles of Ra223. Co-administration of bone-protecting agents (BPAs) 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% confidence interval (CI) 0.60-0.96, P = 0.0096] for OS in favor 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 months) in the enzalutamide arm (n = 224) and 38.2 months (95% CI 33.1-44.8 months) in the combination arm (n = 222). The HR for rPFS was 0.71 (95% CI 0.57-0.89). Grade >= 3 treatment-emergent adverse events (TEAEs) increased from 57.6% to 69.3% in the combination arm, as did treatment-related grade >= 3 TEAEs (18.8% versus 28.9%), with the most frequent being hypertension. Conclusions: 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 BPA is required to reduce skeletal complications.

Filiaciones:
Gillessen, S:
 Oncol Inst Southern Switzerland, EOC, Bellinzona, Switzerland

 Univ Svizzera Italiana, Fac Biosci, Lugano, Switzerland

Gallardo, E:
 Univ Autonoma Barcelona, Parc Tauli Hosp Univ, Inst Invest & Innovacio Parc Tauli I3PT CERCA, Sabadell, Spain

Choudhury, A:
 Univ Manchester, Div Canc Sci, Manchester, England

 Christie NHS Fdn Trust, Manchester, England

Saad, F:
 Ctr Hosp Univ Montreal, Montreal, PQ, Canada

Soares, A:
 Einstein Hosp Israelita, Sao Paulo, Brazil

Loriot, Y:
 Univ Paris Saclay, Gustave Roussy, Predicteurs Mol & Nouvelles Cibles Oncol, INSERM, Paris, France

McDermott, R:
 St Vincents Univ Hosp, Dublin, Ireland

Rodriguez-Vida, A:
 Hosp del Mar, Barcelona, Spain

Velho, PI:
 Moinhos Vento Hosp, Porto Alegre, Brazil

Nolè, F:
 IRCCS, Ist Europeo Oncol, Milan, Italy

Cruz, F:
 Inst Brasileiro Controle Canc, Sao Paulo, Brazil

Roumeguere, T:
 Hop Erasme, HUB, Brussels, Belgium

Daugaard, G:
 Copenhagen Univ Hosp, Rigshosp, Copenhaghen, Denmark

Yamamura, R:
 Beneficencia Portuguesa Sao Paulo, Sao Paulo, Brazil

Bompas, E:
 Inst Cancerol Ouest, St Herbain, France

Maroto, P:
 Hosp Santa Creu & Sant Pau, Barcelona, Spain

Veiga, FG:
 CHUAC A Coruna CAUSA, Salamanca, Spain

Skoneczna, I:
 Maria Sklodowska Curie Mem Canc Ctr, Warsaw, Poland

da Trindade, KM:
 Inst DOr Pesquisa & Ensino, Rio De Janeiro, Brazil

Carcano, FM:
 Hosp Canc Barretos, Barretos, Brazil

Lecouvet, F:
 Clin Univ St Luc, Brussels, Belgium

 Inst Canc Roi Albert II IRA2, Brussels, Belgium

Coens, C:
 European Org Res Treatment Canc, Brussels, Belgium

Poncet, C:
 European Org Res Treatment Canc, Brussels, Belgium

Fournier, B:
 European Org Res Treatment Canc, Brussels, Belgium

Tombal, B:
 Clin Univ St Luc, Brussels, Belgium

 Inst Canc Roi Albert II IRA2, Brussels, Belgium
ISSN: 09237534





ANNALS OF ONCOLOGY
Editorial
ELSEVIER, RADARWEG 29, 1043 NX AMSTERDAM, NETHERLANDS, Reino Unido
Tipo de documento: Article
Volumen: 37 Número: 5
Páginas: 736-742
WOS Id: 001750116600001
ID de PubMed: 41763609
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