Multicenter, Randomized, Phase II Trial of Olaparib Plus Radium-223 Versus Radium-223 in Men With Castration-Resistant Prostate Cancer With Bone Metastases (COMRADE)

PURPOSE: Radium-223 is an α-emitting radiopharmaceutical that improves survival in metastatic castration-resistant prostate cancer (mCRPC). Preclinical data suggest synergy between poly(ADP-ribose) polymerase (PARP) inhibition and radiation. After phase I dose-finding, we conducted a randomized phase II trial to assess efficacy and safety of this combination versus radium-223. PATIENTS AND METHODS: Men with mCRPC and ≥2 bone metastases (BM) were randomly assigned 1:1 to olaparib (200 mg twice daily) plus radium-223 (55 kBq/kg intravenous once every 4 weeks × 6 doses) or radium-223. Crossover was allowed at progression. The primary end point was investigator-assessed radiographic progression-free survival (rPFS). RESULTS: 3.6%). CONCLUSION: Olaparib plus radium-223 significantly prolonged rPFS compared with radium-223 in men with mCRPC and BM. Despite increased hematologic toxicity, the regimen was manageable and supports further exploration of DNA damage-targeted strategies in this population.