Enzalutamide plus radium-223 in metastatic castration-resistant prostate cancer: results of the EORTC 1333/PEACE-3 trial
Por:
Tombal, B, Choudhury, A, Saad, F, Gallardo, E, 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, Trindade, KMD, Carcano, FM, Lecouvet, F, Coens, C, Poncet, C, Fournier, B, Gillessen, S, Crua, F
Publicada:
1 sep 2025
Ahead of Print:
1 ago 2025
Resumen:
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.
Filiaciones:
Tombal, B:
Clin Univ St Luc, Brussels, Belgium
Clin Univ St Luc, Serv Urol, Ave Hippocrate 10, B-1200 Brussels, Belgium
Choudhury, A:
Christie NHS Fdn Trust, Manchester, England
Saad, F:
Ctr Hosp Univ Montreal, Montreal, PQ, Canada
Gallardo, E:
Univ Autonoma Barcelona, Parc Tauli Hosp Univ, Inst Invest & Innovacio Parc Tauli I3PT CERCA, Sabadell, Spain
Soares, A:
Hosp Israelita Albert Einstein, Sao Paulo, Brazil
Loriot, Y:
Inst Gustave Roussy, Paris, France
Univ Paris Saclay, Paris, France
Rodriguez-Vida, A:
Hosp del Mar, Barcelona, Spain
Velho, PI:
Moinhos de Vento Hosp, Porto Alegre, Brazil
Nolè, F:
Ist Europeo Oncol IRCCS, IEO, Milan, Italy
Cruz, F:
Inst Brasileiro Controle Canc, Sao Paulo, Brazil
Roumeguere, T:
Hop Erasme, HUB, Brussels, Belgium
Daugaard, G:
Rigshosp, Copenhagen, 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
Trindade, KMD:
Inst DOr Pesquisa Ensino, Rio De Janeiro, Brazil
Carcano, FM:
Hosp Canc Barretos, Barretos, Brazil
Lecouvet, F:
Clin Univ St Luc, 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
Gillessen, S:
Oncol Inst Southern Switzerland, EOC, Bellinzona, Switzerland
Univ Svizzera Italiana, Fac Biosci, Lugano, Switzerland
Tallaght Univ Hosp, Dublin, Ireland
Green Submitted, hybrid
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