Findings from the phase 3 PEACE-3 trial demonstrate the addition of 6 cycles of Ra223 to enzalutamide in the first-line treatment of metastatic castration-resistant prostate cancer significantly improves radiological progression-free survival (PFS) vs enzalutamide alone.

These results were presented by Silke Gillessen, MD, Department of Medical Oncology of the Università della Svizzera Italiana and Oncology Institute of Southern Switzerland, Bellinzona, at the 2024 ESMO Congress in Barcelona, Spain.

PEACE-3 is a phase 3 cooperative study investigating whether the addition of Ra223 to enzalutamide improves cancer progression among asymptomatic or mildly symptomatic

patients with bone metastatic castration-resistant prostate cancer vs enzalutamide alone.

The trial enrolled 446 patients between November 2015 to March 2023. The median age of patients was 70 years. The median follow-up duration was 42.2 months and 87.9% of patients in the enzalutamide plus Ra223 arm who started Ra223 completed the scheduled 6 cycles.

The hazard ratio (HR) for radiological PFS was 0.69 (95% confidence interval [CI], 0.54 to 0.87; P = .0009), with a median radiological PFS of 16.4 months (95% CI, 13.8 to 19.2) in the enzalutamide alone arm and 19.4 months (95% CI, 17.1 to 25.3) in the enzalutamide plus Ra223 arm.

The HR for overall survival (OS) was 0.69 (95% CI, 0.52 to 0.90; P = .0031), with median OS in the preplanned interim analysis, performed at 80% of events, of 35 months (95% CI, 28.8 to 38.9) in the enzalutamide alone arm and 42.3 months (95% CI, 36.8 to 49.1) in the enzalutamide plus Ra223 arm. It was noted that due to non-proportionality, the study will proceed to final OS analysis.

Regarding safety, treatment-emergent adverse events (AEs) grade ≥1 were reported in 96.4% of patients in the enzalutamide alone arm and 100% of patients in the enzalutamide plus RA223. Grade ≥3 treatment-emergent AEs were reported in 55.8% and 65.6% of the patients, respectively.

The most common grade ≥3 treatment-emergent AEs in the enzalutamide plus Ra223 arm were hypertension (34%), fatigue (6%), anemia (5%), and neutropenia (5%). There were no grade ≥3 AEs that increased by more than 5% in the enzalutamide plus Ra223 arm vs the enzalutamide arm.

In conclusion, the PEACE-3 trial showed that adding 6 cycles of Ra223 to enzalutamide as first-line therapy for metastatic castration-resistant prostate cancer significantly improves radiological PFS.

“An interim analysis shows a statistically significant OS benefit favoring the enzalutamide plus Ra223, and a final OS analysis will be performed for further confirmation of this result,” concluded Dr Gillessen.

Source:

Gillessen S, Choudhury A, Saad F, 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. Presented at 2024 ESMO Congress. September 13-17, 2024. Abstract LBA1