Purpose <p>The comparative real-world adverse event (AE) reporting profiles of enzalutamide, olaparib, and lutetium Lu-177 vipivotide tetraxetan remain incompletely characterized in prostate cancer. As sequential and combination strategies continue to evolve, understanding post-marketing AE reporting patterns in broader clinical populations is important. This study aimed to characterize time-dependent AE reporting profiles and descriptively summarize sparse reports involving concomitant use of all three agents using a large pharmacovigilance database.</p> Methods <p>We performed a retrospective disproportionality analysis of the FDA Adverse Event Reporting System (FAERS) database from each drug’s approval date through the third quarter of 2025. Reports were included when the drug of interest was listed as the primary suspect drug and prostate cancer was recorded as the therapeutic indication. Signal detection used four algorithms: reporting odds ratio (ROR), proportional reporting ratio (PRR), multi-item gamma Poisson shrinker (MGPS), and Bayesian confidence propagation neural network (BCPNN). Stratified analyses by age and time-to-onset were conducted, and reports involving concomitant use of all three agents were summarized descriptively.</p> Results <p>A total of 8,341 enzalutamide, 217 olaparib, and 486 lutetium Lu-177 vipivotide tetraxetan primary-suspect reports with prostate cancer as the indication were included. Distinct AE reporting patterns were observed across the three individual-drug cohorts. Olaparib showed a strong disproportionality signal for anaemia (ROR 8.77), whereas lutetium Lu-177 vipivotide tetraxetan was characterized by signals for dry mouth (ROR 18.08) and thrombocytopenia. Time-to-onset analysis showed that many reported AEs occurred within the first 90 days after treatment initiation. Seven reports involved concomitant use of all three agents; this subset was too sparse to support reliable signal detection or inference regarding drug-drug interaction.</p> Conclusion <p>This study provides a comparative overview of post-marketing AE reporting patterns for three major prostate cancer therapies. The findings were broadly consistent with established toxicity profiles and suggested that early treatment may represent an important period for clinical observation. Because reports involving concomitant use of all three agents were extremely sparse, no reliable conclusions regarding drug-drug interaction, additive toxicity, or synergistic toxicity can be drawn. Prospective studies are needed to characterize the safety of emerging multi-agent treatment strategies. Interpretation of cross-drug comparisons should additionally account for substantial inter-cohort differences in reporter type and reporting country.</p>