Pharmacovigilance signals of androgen receptor pathway inhibitors in non-geriatric men with prostate cancer: A FAERS disproportionality analysis.

Abstract

e17045 Background: Age-restricted real-world safety patterns of androgen receptor pathway inhibitors (ARPIs) in prostate cancer are incompletely characterized. We evaluated adverse event (AE) reporting signals for enzalutamide, abiraterone, apalutamide, and darolutamide in non-geriatric men. Methods: FAERS (Q4/2003–Q3/2025) was queried via OpenVigil 2.1. Included were male patients aged 18–64 years with an ARPI as the primary suspect drug. AEs were analyzed at MedDRA preferred term level. Disproportionality analysis was performed using reporting odds ratio (ROR) with 95% confidence intervals (CI); signals were defined as PRR≥2 and χ²≥4. Results: Among 1,594,913 background cases, 4,570 ARPI cases were identified (abiraterone n = 2,060; enzalutamide n = 1,812; apalutamide n = 394; darolutamide n = 304). Fatigue was reported across all ARPIs, with enzalutamide showing a ROR of 5.48 (4.83, 6.23) (n = 280) and darolutamide a ROR of 4.79 (3.46, 6.64) (n = 42). Rash with apalutamide showed a ROR of 4.65 (3.27, 6.61), and hypertension with apalutamide showed a ROR of 3.44 (2.02, 5.87) . Abiraterone demonstrated signals including long QT syndrome with a ROR of 12.54 (4.67, 33.72), hypokalemia with a ROR of 4.80 (3.12, 7.39) (n = 21), blood pressure increased with a ROR of 2.15 (1.51, 3.07) , and liver function test increased with a ROR of 7.92 (4.75, 13.19) (n = 15). Memory impairment with enzalutamide showed a ROR of 2.23 (1.46, 3.40) (n = 22). Seizure did not meet signal criteria and was not observed with darolutamide. Conclusions: In men aged 18–64 years, ARPIs display distinct FAERS reporting signals that may inform agent-tailored monitoring. Fatigue remains a cross-ARPI signal, including with darolutamide. Findings require validation in prospective studies. Selected disproportionality signals (ROR) for ARPIs. Adverse Event Enzalutamide (N=1,812) Abiraterone (N=2,060) Apalutamide (N=394) Darolutamide (N=304) Fatigue 5.48 (4.82–6.23) 2.80 (2.39–3.26) 3.38 (2.43–4.68) 4.79 (3.46–6.64) Seizure 0.85 (0.52–1.38) 0.32 (0.15–0.68) 0.48 (0.12–1.94) 0 (NA) Rash 0.77 (0.53–1.12) 0.53 (0.35–0.81) 4.65 (3.27–6.61) 2.02 (1.14–3.60) Hypertension 0.83 (0.51–1.36) 1.99 (1.47–2.70) 3.44 (2.02–5.87) 0.93 (0.30–2.90) Asthenia 2.11 (1.63–2.72) 1.69 (1.29–2.20) 1.60 (0.85–3.00) 4.79 (3.11–7.40) Falls 1.54 (1.04–2.26) 2.04 (1.48–2.80) 1.36 (0.56–3.28) 1.41 (0.52–3.77) Cardiac Failure 0.82 (0.37–1.84) 0.56 (0.21–1.50) 0.63 (0.09–4.49) 2.89 (0.93–9.01) Values are ROR (95% CI); n indicates the number of FAERS cases reporting the PT with the ARPI as primary suspect. Disproportionality estimates from FAERS are subject to under-reporting, reporting bias, and confounding; causality cannot be inferred. PTs with very low counts (e.g., n<5) should be interpreted cautiously due to statistical instability and wide uncertainty.