Disproportionality analysis of adverse events associated with tyrosine kinase inhibitors in gastrointestinal stromal tumors in the FDA adverse event reporting system.

Tyrosine kinase inhibitors (TKIs) have revolutionized the treatment of gastrointestinal stromal tumors (GISTs). However, comprehensive real-world comparisons of their safety profiles, temporal patterns, and demographic variations remain limited. This study aims to evaluate and compare the adverse event (AE) landscapes of four FDA-approved TKIs using post-marketing surveillance data. AE reports were extracted from the FDA Adverse Event Reporting System database. Disproportionality analysis, utilizing the reporting odds ratio (ROR), was conducted to identify safety signals. The temporal patterns of AE onset were characterized using Weibull shape parameter analysis. Additionally, subgroup analyses were performed to explore the influence of gender and age on AEs reporting. Imatinib exhibited the most extensive signal spectrum, while Ripretinib has recently surpassed Imatinib in annual reporting volume. Regorafenib demonstrated the shortest median time-to-onset (10.5 days), with a high incidence of palmar-plantar erythrodysesthesia and hypertension. Sunitinib was uniquely associated with endocrine disorders, specifically hypothyroidism. Weibull analysis categorized all four TKIs under an "early failure" pattern, indicating that the highest risk of AEs occurs during the initial treatment phase. Subgroup analyses revealed that males and elderly patients were more prone to hospitalization in patients receiving Ripretinib, whereas younger patients receiving Sunitinib showed a higher likelihood of cardiopulmonary failure. This study delineates distinct safety profiles and temporal risk kinetics for GIST-targeted TKIs. The findings underscore the necessity of intensive early monitoring, particularly for Regorafenib, and suggest that clinical vigilance should be tailored to patient-specific factors to optimize treatment adherence and outcomes.