KEY TAKEAWAYS
- The PEACE phase-III trial aimed to compare the efficacy of Enzalutamide with Ra223 vs Enzalutamide alone in patients with mCRPC.
- The primary endpoint was to determine rPFS.
- Combination of ENZ plus Radium-223 significantly improved both rPFS and OS in mCRPC; further research is ongoing.
The PEACE-III study is a collaboration between EORTC, CTI, CUOG, LACOG, and UNICANCER. Silke Gillessen and the team aimed to determine if combining ENZ with Radium-223 (ENZ-RAD) improves cancer progression compared to Enzalutamide (ENZ) alone in treating patients with metastatic castration-resistant prostate cancer (mCRPC).
Men with mCRPC and bone metastases were randomly assigned to receive ENZ alone or ENZ plus Radium-223. As of March 2018, co-administration of zoledronic acid or denosumab was mandatory for all patients.
The primary endpoint was to measure radiological progression-free survival (rPFS), while secondary endpoints included OS, time to next treatment, pain progression, and first symptomatic skeletal event.
About 446 men were enrolled between November 2015 and March 2023, with a median age of 70. The median follow-up was 42.2 months. In the ENZ-RAD arm, 87.9% of patients completed all 6 cycles who started Ra223.
The HR for rPFS was 0.69 (0.54-0.87, P=0.0009), with median rPFS of 16.4 (13.8-19.2) months in the ENZ arm and 19.4 (17.1-25.3) months in the ENZ-RAD arm. The HR for OS was 0.69 (0.52-0.90, P=0.0031) with a median OS of 35.0 (28.8-38.9) months in the ENZ arm and 42.3 (36.8-49.1) months in the ENZ-RAD arm. Treatment-emergent adverse events (TEAE) occurred in 96.4% (ENZ) and 100% (ENZ-RAD), with ≥ grade 3 events in 55.8% and 65.6% respectively, most commonly hypertension (34%), anemia (5%), neutropenia (5%) and fatigue (6%).
The study concluded that adding 6 cycles of Ra223 to ENZ as the first-line (1L) treatment for mCRPC significantly improved rPFS and demonstrated a statistically significant OS benefit. The final OS analysis is pending further confirmation.
The trial was sponsored by Bayer Healthcare Pharmaceuticals Inc and Astellas Pharma Europe.
Source: https://cslide.ctimeetingtech.com/esmo2024/attendee/confcal/show/session/101
Clinical Trial: https://clinicaltrials.gov/study/NCT02194842
Gilessen S, Choudhury A, Saad F, et al. (2024). “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.” Presented at ESMO 2024 (Abstract LBA1).
