Pharmacovigilance of Androgen Receptor Pathway Inhibitors in Prostate Cancer: The Impact of Docetaxel Co-Reporting

Background/Objectives: Androgen receptor pathway inhibitors (ARPIs) are widely used across prostate cancer disease states, but spontaneous-report safety signals may be distorted by co-administered therapies. We characterized ARPI-associated adverse event reporting in men aged 18-64 years with prostate cancer and tested whether robust signals persisted after accounting for documented docetaxel co-reporting. Methods: We analyzed deduplicated U.S. Food and Drug Administration Adverse Event Reporting System (FAERS) reports from 2014 Q1 through 2026 Q1 in which abiraterone, enzalutamide, apalutamide, or darolutamide was the primary suspect drug. Disproportionality was assessed using ROR, PRR, chi-square, and Bayesian information component metrics. Priority signals were tested across three reference backgrounds, followed by symmetric exclusion of docetaxel-co-reported cases from the darolutamide group and the comparator. Results: Among 19,814 age- and disease-restricted background reports, 4919 involved an ARPI as the primary suspect. Docetaxel was co-reported in 27.8% of darolutamide reports. Darolutamide-associated decreased neutrophil count remained positive across all three reference backgrounds and was IC025-supported, yet both decreased neutrophil count and myelosuppression fell to zero events after documented docetaxel exclusion. Peripheral neuropathy persisted with 20 events. Enzalutamide-associated fatigue and dizziness were more strongly reported in patients aged ≥ 65 years. Conclusions: ARPIs showed distinct adverse event reporting patterns in men aged 18-64 years with prostate cancer. Disappearance of darolutamide-associated hematologic signals after documented docetaxel exclusion highlights the value of regimen-level sensitivity analyses in pharmacovigilance of combination cancer therapies. Persistent peripheral neuropathy requires external evaluation because residual confounding from unreported or prior neurotoxic treatment cannot be excluded.