TY - JOUR
T1 - Decrease in Fracture Rate with Mandatory Bone-protecting Agents in the EORTC 1333/PEACE-3 Trial Comparing Radium-223 Combined with Enzalutamide Versus Enzalutamide Alone
T2 - A Safety Analysis
AU - Gillessen, Silke
AU - Tombal, Bertrand
AU - Turco, Fabio
AU - Choudhury, Ananya
AU - Rodriguez-Vida, Alejo
AU - Gallardo, Enrique
AU - Velho, Pedro Isaacsson
AU - Nolè, Franco
AU - Cruz, Felipe
AU - Loriot, Yohann
AU - McDermott, Ray
AU - Roumeguere, Thierry
AU - Daugaard, Gedske
AU - Yamamura, Rosley
AU - Bompas, Emmanuelle
AU - Maroto, Pablo
AU - Polo, Manuel Herrero
AU - da Trindade, Karine Martins
AU - Preto, Daniel D.Almeida
AU - Skoneczna, Iwona
AU - Lecouvet, Frederic
AU - Coens, Corneel
AU - Fournier, Beatrice
AU - Saad, Fred
N1 - Publisher Copyright:
© 2024 European Association of Urology
PY - 2025/1/1
Y1 - 2025/1/1
N2 - Bone health is central to the management of patients with metastatic castration-resistant prostate cancer (mCRPC). International guidelines recommend giving a bone-protecting agent (BPA) to patients with mCRPC and bone metastases. However, the data supporting these recommendations were generated before androgen receptor pathway inhibitors (ARPIs) were available. Here we publish for the first time fracture rates from an interim safety analysis of the international prospective phase 3 PEACE-3 trial comparing radium-223 (223Ra) combined with enzalutamide for first-line mCPRC to enzalutamide alone. After results from the ERA-223 trial (abiraterone ± 223Ra) showed a high fracture rate in both arms, the independent data monitoring committee of PEACE-3 mandated BPA use during the trial, which increased BPA use from 46.1% to 97%. For patients who received BPA therapy, fracture rates significantly decreased in both study arms. At 1 year, fractures decreased from 15.6% to 2.6% with a BPA in patients receiving enzalutamide monotherapy. The interim safety analysis of PEACE-3 underscores the high risk of fracture in patients with mCRPC and the necessity of complying with guidelines regarding BPA administration in the ARPI era. The EORTC GUCG-1333 PEACE-3 trial is registered on ClinicalTrials.gov as NCT02194842 and on EudraCT as 2014-001787-36.
AB - Bone health is central to the management of patients with metastatic castration-resistant prostate cancer (mCRPC). International guidelines recommend giving a bone-protecting agent (BPA) to patients with mCRPC and bone metastases. However, the data supporting these recommendations were generated before androgen receptor pathway inhibitors (ARPIs) were available. Here we publish for the first time fracture rates from an interim safety analysis of the international prospective phase 3 PEACE-3 trial comparing radium-223 (223Ra) combined with enzalutamide for first-line mCPRC to enzalutamide alone. After results from the ERA-223 trial (abiraterone ± 223Ra) showed a high fracture rate in both arms, the independent data monitoring committee of PEACE-3 mandated BPA use during the trial, which increased BPA use from 46.1% to 97%. For patients who received BPA therapy, fracture rates significantly decreased in both study arms. At 1 year, fractures decreased from 15.6% to 2.6% with a BPA in patients receiving enzalutamide monotherapy. The interim safety analysis of PEACE-3 underscores the high risk of fracture in patients with mCRPC and the necessity of complying with guidelines regarding BPA administration in the ARPI era. The EORTC GUCG-1333 PEACE-3 trial is registered on ClinicalTrials.gov as NCT02194842 and on EudraCT as 2014-001787-36.
KW - Bone fractures
KW - Bone health
KW - Bone-protecting agents
KW - Enzalutamide
KW - Metastatic castration-resistant prostate cancer
KW - Radium-223
KW - Safety analysis
UR - http://www.scopus.com/inward/record.url?scp=85215388866&partnerID=8YFLogxK
U2 - 10.1016/j.eururo.2024.11.027
DO - 10.1016/j.eururo.2024.11.027
M3 - Article
AN - SCOPUS:85215388866
SN - 0302-2838
JO - European Urology
JF - European Urology
ER -