Comparative safety profiles of enzalutamide, olaparib, and lutetium Lu-177 vipivotide tetraxetan in patients with prostate cancer: a real-world disproportionality analysis of the FAERS database.
This study highlights distinct adverse event profiles for enzalutamide, olaparib, and lutetium Lu-177 vipivotide tetraxetan in prostate cancer, with specific signals for anaemia and dry mouth.
Where it sits
this study against the rest of the vipivotide corpusSummary and findings
This study analyzed adverse event reporting profiles of enzalutamide, olaparib, and lutetium Lu-177 vipivotide tetraxetan in prostate cancer using the FAERS database. A total of 8,341 enzalutamide, 217 olaparib, and 486 lutetium Lu-177 vipivotide tetraxetan reports were included. Distinct adverse event patterns were observed, with olaparib showing a strong signal for anaemia and lutetium Lu-177 vipivotide tetraxetan for dry mouth and thrombocytopenia.
Abstract
<h4>Purpose</h4>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.<h4>Methods</h4>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.<h4>Results</h4>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.<h4>Conclusion</h4>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.
Background
This paper addresses the comparative safety profiles of three therapies for prostate cancer: enzalutamide, olaparib, and lutetium Lu-177 vipivotide tetraxetan. Previous studies have characterized adverse events for these agents individually, but comprehensive comparisons in real-world settings are limited. Understanding adverse event reporting patterns is crucial as treatment strategies evolve.
Methods
A retrospective disproportionality analysis of the FDA Adverse Event Reporting System (FAERS) database was conducted from each drug's approval date through the third quarter of 2025. The analysis included reports where the drug was the primary suspect and prostate cancer was the indication. Signal detection utilized four algorithms: ROR, PRR, MGPS, and BCPNN.
Results
A total of 8,341 reports for enzalutamide, 217 for olaparib, and 486 for lutetium Lu-177 vipivotide tetraxetan were analyzed. The ROR for anaemia with olaparib was 8.77, while for lutetium Lu-177 vipivotide tetraxetan, the ROR for dry mouth was 18.08. Many adverse events were reported within the first 90 days of treatment initiation.
Interpretation
The findings align with established toxicity profiles for the drugs, with olaparib and lutetium Lu-177 vipivotide tetraxetan showing specific adverse events. However, the clinical significance of these findings is uncertain due to the nature of the data and potential confounding factors such as reporting biases. The sparse data on concomitant use limits conclusions about drug interactions.
Key findings
- 8,341 enzalutamide reports, 217 olaparib reports, and 486 lutetium Lu-177 vipivotide tetraxetan reports included.
- Olaparib showed a strong disproportionality signal for anaemia (ROR 8.77).
- Lutetium Lu-177 vipivotide tetraxetan characterized by signals for dry mouth (ROR 18.08) and thrombocytopenia.
- Many reported AEs occurred within the first 90 days after treatment initiation.
- Seven reports involved concomitant use of all three agents; too sparse for reliable signal detection.
Limitations
- Retrospective analysis of adverse event reports.
- Sparse reports involving concomitant use of all three agents.
- Potential reporting biases in the FAERS database.
- Short follow-up period for adverse events.