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: A Safety Analysis

Abstract

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.

Keywords: Bone fractures; Bone health; Bone-protecting agents; Enzalutamide; Metastatic castration-resistant prostate cancer; Radium-223; Safety analysis.