Top Line: Does olaparib improve the efficacy of radium-223 for metastatic prostate cancer?
The Study: Radium-223 is indicated for metastatic, castration resistant prostate cancer without visceral metastases. PEACE-3 also recently showed that adding radium-223 to enzalutamide improves overall survival. COMRADE was a randomized phase 2 trial that sought to determine if adding the PARP inhibitor olaparib to radium-223 improved radiographic progression free survival. The idea here is that olaparib inhibits base excision repair and may synergistically enhance DNA damage from radium-223. The trial included 120 patients with mCRPC and at least two bone metastases who were randomized to receive radium-223 with or without olaparib. Most patients had advanced disease with the majority having received prior androgen receptor pathway inhibitor (96%), 52% had prior docetaxel, and 47% had more than 20 bone mets. The addition of olaparib nearly doubled median rPFS (4.7 v 8.9 months). At 1 year, there was also a significantly lower rate of symptomatic skeletal events (12.7% v 22.9%). The combination was particularly effective in those who had prior docetaxel (13.7 v 5.7 months) and those with a lower burden of bone metastases (<20 mets, 4.2 v 13.4 months).
TBL: In this randomized trial, adding olaparib to radium-223 in patients with heavily pretreated mCRPC significantly improved radiographic progression free survival. | McKay, J Clin Oncol 2026
The Study: Radium-223 is indicated for metastatic, castration resistant prostate cancer without visceral metastases. PEACE-3 also recently showed that adding radium-223 to enzalutamide improves overall survival. COMRADE was a randomized phase 2 trial that sought to determine if adding the PARP inhibitor olaparib to radium-223 improved radiographic progression free survival. The idea here is that olaparib inhibits base excision repair and may synergistically enhance DNA damage from radium-223. The trial included 120 patients with mCRPC and at least two bone metastases who were randomized to receive radium-223 with or without olaparib. Most patients had advanced disease with the majority having received prior androgen receptor pathway inhibitor (96%), 52% had prior docetaxel, and 47% had more than 20 bone mets. The addition of olaparib nearly doubled median rPFS (4.7 v 8.9 months). At 1 year, there was also a significantly lower rate of symptomatic skeletal events (12.7% v 22.9%). The combination was particularly effective in those who had prior docetaxel (13.7 v 5.7 months) and those with a lower burden of bone metastases (<20 mets, 4.2 v 13.4 months).
TBL: In this randomized trial, adding olaparib to radium-223 in patients with heavily pretreated mCRPC significantly improved radiographic progression free survival. | McKay, J Clin Oncol 2026