Murilo De Almeida Luz, MD, on PSA and ALP changes with enzalutamide/radium-223

The PEACE-3 trial (NCT02194842) previously demonstrated that adding 6 cycles of radium-223 (Ra-223) to enzalutamide (Xtandi) significantly improves progression-free survival (PFS) and overall survival (OS) vs enzalutamide alone in patients with metastatic castration-resistant prostate cancer (mCRPC) with bone metastases.¹
Additional data from the trial were recently presented at the 2025 American Society of Clinical Oncology Annual Meeting in Chicago, Illinois, looking at changes in prostate-specific antigen (PSA) and alkaline phosphatase (ALP) levels among patients enrolled in the study.²

In an interview with Urology Times®, Murilo De Almeida Luz, MD, discussed the background for the PEACE-3 trial and shared key findings from this exploratory analysis. Luz is a urologic oncologist at Mount Sinai Icahn School of Medicine in New York, New York.

Overall, data from the analysis showed that 77.1% and 76.8% of patients in the enzalutamide/ra-223 arm achieved a PSA decline of at least 50% at 6- and 12-months, respectively, compared with 69.9% and 66.2% of patients in the enzalutamide monotherapy arm. Additionally, a PSA decline of at least 90% at 6- and 12-months was achieved in 50.5% and 54.9% of patients in the combination arm vs 34.1% and 37.6% of patients in the monotherapy arm, respectively.

In looking at ALP response rates, a decline of at least 30% at 6- and 12-months was achieved in 56.5% and 50.0% of patients in the combination arm vs 50.8% and 47.4% in the monotherapy arm, respectively. ALP normalization rates at the 6- and 12-month timepoints were 76.2% and 77.45% in the enzalutamide/ra-223 arm and 50.5% and 61.3% in the enzalutamide alone arm, respectively.

Based on these data, Luz concluded, “I think this is pretty reassuring that we're doing a good job in having that combination of enzalutamide and radium-223, of course, with the first concerns [being] about the safety this combination. We know it's safe, especially using the bone protecting agents, which is very important to mention.”

REFERENCES

1. Tombal B, Choudhury A, Saad F, et al. Enzalutamide plus radium-223 in metastatic castration-resistant prostate cancer: results of the EORTC 1333/PEACE-3 trial. Ann Oncol. 2025:S0923-7534(25)00203-0. doi:10.1016/j.annonc.2025.05.011

2. Choudhury A, Gillessen S, Saad F, et al. PSA and alkaline phosphatase changes in the EORTC-1333 PEACE-3 study evaluating the addition of six cycles of radium 223 in metastatic castration-resistant prostate cancer (mCRPC) starting enzalutamide. J Clin Oncol. 2025;43 (suppl 16, abstr 5062). doi:10.1200/JCO.2025.43.16_suppl.5062