Olaparib Plus Radium-223 Improves rPFS in COMRADE

Key Takeaways

• Olaparib plus radium-223 was associated with longer investigator-assessed radiographic progression-free survival than radium-223 alone.
• Longer radiographic progression-free survival was most pronounced without prior docetaxel and with 20 or fewer bone metastases, and symptomatic skeletal-related events were less frequent at 1 year.
• Median overall survival was similar between groups, while grade 3 or higher treatment-related adverse events were more frequent and were mainly hematologic.

Men with metastatic castration-resistant prostate cancer and bone metastases had longer radiographic progression-free survival with olaparib plus radium-223 than with radium-223 alone in the COMRADE randomized phase II trial. The primary endpoint was investigator-assessed radiographic progression-free survival, with a median of 8.9 versus 4.7 months and an HR of 0.50.

COMRADE followed a prior phase I dose-finding study as a multicenter randomized phase II trial. The study randomly assigned 120 men with mCRPC and at least 2 bone metastases in a 1:1 ratio across the two groups. Treatment consisted of olaparib 200 mg twice daily plus radium-223 55 kBq/kg intravenously every 4 weeks for 6 doses, or radium-223 alone. Crossover was allowed at progression, most patients had prior androgen receptor pathway inhibitor exposure, and 52% had previously received docetaxel. 47% had more than 20 bone metastases, and 90% received bone-protecting agents.

Among men without prior docetaxel, median rPFS was 13.7 versus 5.7 months, with an HR of 0.24 and a 90% CI of 0.15 to 0.40. Among those with 20 or fewer bone metastases, median rPFS was 13.4 versus 4.2 months, with an HR of 0.21 and a 90% CI of 0.13 to 0.33. The 1-year cumulative incidence of symptomatic skeletal-related events was 12.7% with the combination and 22.9% with radium-223 alone.

Median overall survival was similar between groups at 20.2 months with the combination and 21.1 months with radium-223 alone. Grade 3 or higher treatment-related adverse events occurred in 56% and 33%, respectively, and were mainly hematologic. Reported hematologic events included lymphopenia in 31% versus 9.1%, anemia in 22% versus 16%, and thrombocytopenia in 6.8% versus 3.6%. Investigators reported significant prolongation of rPFS and described the regimen as manageable despite increased hematologic toxicity in this randomized phase II study.