COMRADE Trial: Olaparib Plus Radium-223 Improves rPFS Survival in CRPC
In an interview, Rana McKay, MD, discusses findings from the COMRADE trial evaluating olaparib plus radium-223 in prostate cancer presented at the 2025 ASCO Annual Meeting.
The COMRADE trial, a phase 1/2 study, demonstrated that combining olaparib (Lynparza) with radium-223 (Xofigo)significantly improved radiographic progression-free survival (rPFS) in men with castration-resistant prostate cancer (CRPC) compared to radium-223 alone. These findings, presented at the 2025 American Society of Clinical Oncology (ASCO) Annual Meeting, hold true regardless of the patient's hormone recombination repair (HRR) status.
Rana McKay, MD, medical oncologist at the University of California San Diego, discussed the study in an interview with Targeted OncologyTM.
In the phase 2 portion of the study, the median rPFS was 8.9 months in the combination arm vs 4.7 months in the control arm, representing a statistically significant improvement. This benefit was particularly notable in patients who had not received prior docetaxel treatment and those with 20 or fewer bone metastases.
It is noteworthy, according to McKay, that the original phase 3 trial for radium-223 approval focused on overall survival (OS), reporting approximately 14 months with monotherapy. In contrast, the COMRADE study observed a dramatically longer median OS of around 20 to 21 months in both treatment arms. This extended survival is likely multi-factorial. Our trial permitted crossover, with 23 patients moving from the monotherapy to the combination arm, potentially influencing OS outcomes. Furthermore, over 70% of patients received subsequent therapies, including chemotherapy and lutetium PSMA-based treatments, which are believed to have contributed to the improved overall survival.
Regarding safety, the combination arm showed a higher rate of grade 3 or higher treatment-related adverse events (56% vs 33% in the radium-223 arm), primarily driven by an increased incidence of lymphocytopenia, which was generally manageable. The study concludes that the combination of olaparib and radium-223 is feasible, safe, and exhibits antitumor activity in CRPC patients with bone metastases.
