In a phase II trial (COMRADE) reported in the Journal of Clinical Oncology, McKay et al found that the addition of olaparib to radium-223 improved radiographic progression–free survival in men with castration-resistant prostate cancer and bone metastases.
Study Details
In the U.S. multicenter trial, 120 patients with at least two bone metastases were randomly assigned between March 2021 and January 2024 to receive olaparib at 200 mg twice daily plus radium-223 at 55 kBq/kg once every 4 weeks for six doses (n = 61) or radium-223 alone (n = 59). Crossover was allowed at disease progression. A total of 96% of patients had prior androgen receptor pathway inhibitor exposure, 52% had received docetaxel, 47% had more than 20 bone metastases, and 90% were receiving bone-protecting agents. The primary endpoint was investigator-assessed radiographic progression–free survival.
Key Findings
Median investigator-assessed radiographic progression–free survival was 8.9 months (95% confidence interval [CI] = 5.4–13.7 months) in the olaparib plus radium-223 group vs 4.7 months (95% CI = 3.2–6.0 months) in the radium-223 group (hazard ratio [HR] = 0.50, 90% CI = 0.35–0.70, P = .0042). Pronounced radiographic progression–free survival benefits for the combination were observed among patients without prior docetaxel (median = 13.7 vs 5.7 months; HR = 0.24, 90% CI = 0.15–0.40) and patients with 20 or fewer bone metastases (median = 13.4 vs 4.2 months; HR = 0.21, 90% CI = 0.13–0.33).
The 1-year cumulative incidence of symptomatic skeletal-related events was 12.7% in the combination group vs 22.9% in the radium-223 group.
A total of 23 patients crossed over from the radium-223 group to the combination group at disease progression. Subsequent treatment was received by 28 patients in the olaparib plus radium-223 group and 34 in the radium-223 group. Median overall survival was 20.2 months in the combination group vs 21.1 months in the radium-223 group.
Grade ≥ 3 treatment-related adverse events occurred in 56% of the olaparib plus radium-223 group vs 33% of the radium-223 group; these adverse events were primarily hematologic, including lymphopenia (31% vs 9.1%), anemia (22% vs 16%), and thrombocytopenia (6.8% vs 3.6%). No treatment-related deaths were observed.
The investigators concluded: “Olaparib plus radium-223 significantly prolonged [radiographic progression–free survival] compared with radium-223 in men with [metastatic castration-resistant prostate cancer] and bone metastases. Despite increased hematologic toxicity, the regimen was manageable and supports further exploration of DNA damage–targeted strategies in this population.”
Rana R. McKay, MD, FASCO, of University of California San Diego, La Jolla, California, is the corresponding author for the Journal of Clinical Oncology article.
DISCLOSURE: The study was supported by the Prostate Cancer Foundation and National Institutes of Health. For full disclosures of the study authors, visit ascopubs.org.
