Real-world analysis of androgen receptor inhibitors in US patients with nonmetastatic castration-resistant prostate cancer: DEAR-EXT study.

[BACKGROUND] The real-world retrospective DEAR study in patients with nonmetastatic castration-resistant prostate cancer (nmCRPC) demonstrated darolutamide was associated with lower risks of discontinuation and progression to metastatic castration-resistant disease vs enzalutamide and apalutamide. This analysis expands on DEAR, including additional patients and follow-up, comparing prostate-specific antigen (PSA) response, metastasis-free survival (MFS), and overall survival (OS).

[METHODS] DEAR-EXT was a chart review of electronic medical records from patients in US urology practices who initiated androgen receptor inhibitors (ARIs) for nmCRPC from August 2019-March 2023. Outcomes included time to initial drug discontinuation, time to metastatic castration-resistant prostate cancer (mCRPC), PSA response, MFS, OS, and safety. Adjusted Cox proportional hazards models were used for the primary analysis and inverse probability of treatment weighting and other sensitivity analyses were performed to evaluate the impact of potential selection bias and confounding factors.

[RESULTS] Patients (N = 1375) received darolutamide (n = 565, 41%), enzalutamide (n = 609, 44%), or apalutamide (n = 201, 15%). Baseline characteristics were mainly similar across groups. Adjusted risk of discontinuation was significantly lower with darolutamide vs enzalutamide (hazard ratio [HR] 0.73, 95% confidence interval [CI] 0.61-0.88) and vs apalutamide (HR 0.69, 95% CI 0.54-0.89). Adjusted risk of progression to mCRPC was lower with darolutamide vs enzalutamide (HR 0.63, 95% CI 0.50-0.80) and vs apalutamide (HR 0.72, 95% CI 0.53-0.98). MFS was significantly longer for darolutamide vs enzalutamide (HR 0.65, 95% CI 0.53-0.79) and vs apalutamide (HR 0.72, 95% CI 0.55-0.93). The estimated MFS rates at 24/36 months were 72.3%/60.2% with darolutamide, 59.2%/48.3% with enzalutamide, and 63.9%/47.6% with apalutamide. Darolutamide appeared to be associated with higher PSA response, improved survival, and fewer adverse events vs other ARIs in a real-world setting. Results were consistent in a sensitivity analysis.

[CONCLUSION] Darolutamide demonstrated lower discontinuation rates, longer time to progression, and longer MFS vs other ARIs, highlighting its potential to enhance real-world patient outcomes.

[CLINICAL TRIAL REGISTRATION] ClinicalTrials.gov identifier: NCT06013475.