Editor’s Note: Dr. Enrique Gallardo from Parc Taulí University Hospital (Autonomous University of Barcelona) presented the final overall survival (OS) results of the phase 3 EORTC 1333/PEACE III trial (Abstract 15). The highly anticipated presentation detailed the efficacy and safety of combining enzalutamide with Radium-223 (Ra-223) in patients with metastatic castration-resistant prostate cancer (mCRPC) and bone metastases.01 Study Design: Strategic Combination with Bone Protection
The randomized 1:1 trial enrolled 446 mCRPC patients with bone metastases (asymptomatic or mildly symptomatic, lacking visceral metastases). Patients received either enzalutamide plus six cycles of Ra-223 or enzalutamide alone. Following earlier safety signals in the prostate cancer landscape, the concurrent administration of bone-protecting agents (BPAs) was made mandatory in this study to mitigate fracture risks.
02 Efficacy: Significant Overall Survival Benefit
With a median follow-up of 58 months, the combination therapy met its secondary endpoint by demonstrating a statistically significant and clinically meaningful OS improvement. The median OS was notably extended to 42.3 months in the combination arm compared to 35.0 months in the enzalutamide monotherapy arm (HR=0.69; P=0.0031). Furthermore, survival at 36 months favored the combination (54% vs. 47%). The study also confirmed a sustained improvement in radiographic progression-free survival (rPFS), reinforcing the durability of this synergistic approach.
03 Safety Profile: Manageable Toxicity
The safety analysis revealed a moderate, manageable increase in toxicity. Grade 3-5 drug-related adverse events (AEs) were reported in 29% of patients receiving the combination versus 19% in the control group. Importantly, there were no drug-related deaths. Discontinuation rates due to toxicity remained low in both arms, and no individual adverse event demonstrated an incidence increase of more than 5% in the combination group.
Conclusion & Future Perspectives Dr. Gallardo concluded that the robust OS benefit, coupled with a predictable safety profile, establishes the combination of enzalutamide, Ra-223, and a BPA as a highly valid, evidence-based first-line treatment option for mCRPC patients burdened by bone metastases.
