Real-world comparison of enzalutamide and darolutamide for non-metastatic castration-resistant prostate cancer: A multicenter retrospective study.

e17048 Background: Although enzalutamide and darolutamide share a common mechanism of action targeting the androgen receptor pathway, they differ in their molecular structure and pharmacological properties, which may influence their efficacy and safety. However, real-world evidence directly comparing these agents in patients with non-metastatic castration-resistant prostate cancer (nmCRPC) remains limited. Methods: In this multicenter retrospective study, data from 198 patients who received enzalutamide or darolutamide as their first androgen receptor signaling inhibitor (ARSI) during treatment for nmCRPC, were analyzed. Adverse events (AEs) and prostate-specific antigen (PSA) responses were compared. Progression of PSA and development of metastases were assessed using the Fine-Gray sub-distribution hazards model, adjusting for death as a competing risk. Results: In the cohort, 94 (47%) patients received enzalutamide and 104 (53%) received darolutamide. Incidence rates of any-grade AEs and grade ≥3 AEs were similar between the two groups ( P = 0.968 and P = 1.000, respectively). The rates of any PSA response, decline in PSA ≥50%, and decline in PSA ≥90% did not differ significantly between the two groups ( P = 0.130, P = 0.687, and P = 0.171, respectively). In multivariable analyses, ARSI type was not significantly associated with progression of PSA (reference, enzalutamide; sub-distribution hazard ratio SHR, 1.153; P = 0.620) or development of metastases (reference, enzalutamide; SHR, 0.815; P = 0.510). Conclusions: Enzalutamide and darolutamide had comparable safety and oncological outcomes in patients with nmCRPC. These findings support the use of either agent as an appropriate first ARSI treatment. Multivariable analysis for progression of PSA. Factor P value SHR 95% CI Biopsy Gleason score ≥8 0.120 1.857 0.859–4.015 Clinical stage at initial diagnosis cT4 or cN1 0.420 1.290 0.694–2.397 History of radical treatment Positive 0.073 0.594 0.036–1.051 Number of therapies prior to ARSI treatment Continuous 0.210 1.197 0.903–1.588 PSA doubling time <3.3 months 0.078 1.606 0.949–2.720 Relative dose intensity Continuous 0.660 1.377 0.325–5.831 ARSI type Darolutamide 0.620 1.153 0.659–2.018 ARSI, androgen receptor signaling inhibitor; CI, confidence interval; PSA, prostate-specific antigen; SHR, sub-distribution hazard ratio.