COMPELLING new results from the PEACE-3 trial, were presented recently at the 2024 ESMO conference. This study indicates that combining Enzalutamide (ENZ) with Radium223 (Ra223) significantly improves progression-free survival (PFS) in patients with metastatic castration-resistant prostate cancer (mCRPC) and bone metastases over Enzalutamide alone.
Prostate cancer requires androgen to grow and metastasize. In this trial, researchers investigated whether combination of Ezalutamide, an androgen inhibitor, and Ra223, a type of radiotherapy treatment, improved cancer progression over Enzalutamide alone. Between 2015 and 2023, 446 men with mCRPC were enrolled, with a median age of 70 (IQR: 65-76). After a median follow-up of 42.2 months, the study reported that 87.9% of patients in the ENZ-RAD arm completed the scheduled treatment of six cycles of Ra223. The median radiological PFS was 16.4 months in the ENZ-RAD group compared to 14.0 months for those receiving Enzalutamide alone (hazard ratio [HR]: 0.69, 95% CI: 0.54-0.87, p=0.0009).
Moreover, the combination therapy showed significant benefits in overall survival. The median OS (HR: 0.69; 95%CI: 0.52-0.90; p=0.0031) in the pre-planned interim analysis was 35.0 months for the Enzalutamide only group (95%CI: 28.8-38.9), compared to 42.3 (95%CI: 36.8-49.1) months for the ENZ-RAD arm.
Adverse events were reported in both groups, with 96.4% of patients in the ENZ arm and 100% in the ENZ-RAD group experiencing grade 1 or 2 treatment-emergent adverse events. The most frequent grade 3 side effects in the ENZ-RAD arm included hypertension (34%) and fatigue (6%).
The PEACE-3 trial’s findings show that six treatment cycles of Ra223 to enzalutamide as first-line therapy for mCRPC improved radiological progression-free survival in patients with mCRPC. Following on from the interim analysis results, a final overall survival analysis will be performed to confirm the efficacy and safety of this combination therapy.
Helena Bradbury, EMJ
Reference
Gillessen S et al. A randomized multicenter open label phase III trial comparing enzalutamide vs a combination of Radium-223 (Ra223) and enzalutamide in asymptomatic or mildly symptomatic patients with bone metastatic castration-resistant prostate cancer (mCRPC): First results of EORTC-GUCG 1333/PEACE-3. ESMO 2024. ESMO Annual Meeting, 13-17 September, 2024.
