Real-world Effectiveness of Darolutamide in Patients With nmCRPC

Results from the prespecified third interim analysis of the darolutamide observational (DAROL) study indicate real-world effectiveness with no new safety signals in patients with non-metastatic castration-resistant prostate cancer (nmCRPC).

These results were presented by Andrew Armstrong, MD, MSc, and colleagues at the 2024 American Urological Association Annual Meeting.

The phase 3 ARAMIS study previously showed that darolutamide may significantly improve metastasis-free survival (MFS) by approximately 2 years and reduce the risk of death by 31% compared with placebo in patients with nmCRPC, along with a favorable safety profile.

DAROL was designed to assess the real-world safety and effectiveness of darolutamide in patients with this diagnosis. The ongoing, global, open-label, single-arm, nonobservational trial includes 550 patients aged at least 18 years for whom treatment with darolutamide was decided pre-enrollment.

The primary end point of the study is safety, including incidence and severity of treatment-emergent adverse events (TEAEs). Among the secondary end points are MFS, overall survival (OS), prostate-specific antigen (PSA) progression, and PSA response.

The prespecified interim analysis was conducted after all patients completed at least 6 months of treatment. The data cutoff was July 17, 2023. All patients were assessed for safety, and researchers evaluated effectiveness in patients who had at least 1 postbaseline assessment.

Dr. Armstrong and colleagues noted that the median baseline PSA was 4 ng/mL, with 18.7% of patients having PSA <2 ng/mL. The median PSA doubling time (PSADT) was 5.3 months, and 44.4% of evaluable patients had a PSADT of at least 6 months.

After a median follow-up of 16.5 months and median treatment duration of 14.9 months, incidences of TEAEs and darolutamide-related TEAEs were reportedly low and consistent with those reported in ARAMIS. Additionally, researchers found that OS and MFS rates at 2 years were 87.6% (95% CI, 82.3-91.4) and 78.3% (95% CI, 72.7-83.0), respectively.

The overall PSA progression-free rate at 2 years was 85.3% (95% CI, 79.5-89.5), and 79.4%, 76.0%, and 53.8% of patients had PSA reduction from baseline of 30.0%, 50.0%, and 90.0%, respectively.

“In DAROL, MFS, OS, and PSA outcomes indicated effectiveness in the real-world setting, consistent with ARAMIS,” study authors concluded.