Top Line: Does radium-223 improve survival when added to enzalutamide for metastatic prostate cancer?
The Study: ADT plus an androgen receptor pathway inhibitor is a common first line treatment for metastatic castration resistant prostate cancer (mCRPC). PEACE-3 was a phase 3 trial that randomized 446 patients with mCRPC and at least 2 bone metastases to receive enzalutamide with or without 6 cycles of radium-223. Visceral disease was not allowed, but lymph node metastases were, and just under a third of patients had extraskeletal disease. The study was amended to require a bone protective agent during treatment. We’ve previously seen that the addition of radium-223 significantly prolonged radiographic PFS (median 19.4 v 16.4 months). Now, we have final results that show the addition of radium-223 also significantly improved overall survival (median 38.2 v 32.6 months). Overall, the rate of fractures was higher with enzalutamide plus radium (27.1% v 14.3%), however this was significantly reduced in both arms when bone protective agents were mandated during the trial. After BPA’s were added, fractures went from 20.3% to 12.1% in the enzalutamide arm and 53.6% to 17.9% in the combination arm. The rate of osteonecrosis of the jaw was higher in the radium arm (6.4% v 1.3%).
TBL: Adding radium-223 to enzalutamide for patients with mCRPC (without visceral mets) significantly improves overall survival. | Gillessen, Ann Oncol 2026
The Study: ADT plus an androgen receptor pathway inhibitor is a common first line treatment for metastatic castration resistant prostate cancer (mCRPC). PEACE-3 was a phase 3 trial that randomized 446 patients with mCRPC and at least 2 bone metastases to receive enzalutamide with or without 6 cycles of radium-223. Visceral disease was not allowed, but lymph node metastases were, and just under a third of patients had extraskeletal disease. The study was amended to require a bone protective agent during treatment. We’ve previously seen that the addition of radium-223 significantly prolonged radiographic PFS (median 19.4 v 16.4 months). Now, we have final results that show the addition of radium-223 also significantly improved overall survival (median 38.2 v 32.6 months). Overall, the rate of fractures was higher with enzalutamide plus radium (27.1% v 14.3%), however this was significantly reduced in both arms when bone protective agents were mandated during the trial. After BPA’s were added, fractures went from 20.3% to 12.1% in the enzalutamide arm and 53.6% to 17.9% in the combination arm. The rate of osteonecrosis of the jaw was higher in the radium arm (6.4% v 1.3%).
TBL: Adding radium-223 to enzalutamide for patients with mCRPC (without visceral mets) significantly improves overall survival. | Gillessen, Ann Oncol 2026