Comparative safety profiles of lutetium-177 and enzalutamide: A pharmacovigilance study and disproportionality analysis using real world data.

Abstract

e15136 Background: Lutetium-177 represents a significant advancement in treating metastatic castration-resistant prostate cancer (mCRPC), showing a favorable safety profile characterized primarily by mild to moderate nausea and fatigue. Despite its recent approval and focus on these primary adverse effects, conducting a comprehensive pharmacovigilance study using the FDA Adverse Event Reporting System (FAERS) data for Lutetium-177 remains essential. This study aims to compare the safety profiles of Lutetium-177 and another mCRPC treatment, Enzalutamide. Methods: This pharmacovigilance study utilized FAERS data from the database's inception up to January 2025 to assess the adverse effects (AEs) of Lutetium-177 and Enzalutamide. Descriptive statistics were employed to analyze demographics, AEs, and outcomes, comparing the results for both drugs. A disproportionality analysis was conducted using three complementary signal detection methods: Reporting Odds Ratio (ROR), Proportional Reporting Ratio (PRR), and Empirical Bayes Geometric Mean (EBGM). To ensure the robustness and clinical relevance of identified safety signals, stringent criteria were implemented: ROR—upper bound of 95% Confidence Interval (CI) < 1; PRR—χ2 < 4, PRR < 2, and cases > 3; EBGM—lower bound of 90% CI (EB05) < 1. Results: From inception to January 2025, there were 11,593 reported cases of Lutetium-177 and 51,805 cases of Enzalutamide. After excluding non-specific reactions, the most common adverse effects for both drugs were fatigue and nausea. For fatigue, the ROR was 0.119 (95% CI: 0.125-0.158), the PRR was 0.141, and the EBGM was 0.207. For nausea, the ROR was 0.358 (95% CI: 0.244-0.522), the PRR was 0.373, and the EBGM was 0.363. The table presents the outcomes associated with the use of Lutetium-177. Conclusions: The disproportionality analysis indicated that Lutetium-177 exhibited lower ROR, PRR, and EBGM for fatigue and nausea compared to Enzalutamide, suggesting a potentially lower association of these specific adverse effects with Lutetium-177. Outcomes associated with the use of Lutetium-177. Frequency Percent Died 1614 14.2 Disabled 42 0.4 Hospitalized 658 5.8 Life Threatening 52 .5 Non-Serious 7760 68.4 Other Outcomes 1220 10.8 Total 11346 100.0