Adverse Reactions of First‐Line Tyrosine Kinase Inhibitors in Advanced Hepatocellular Carcinoma Treatment: A Descriptive Analysis From WHO‐VigiAccess

<b>Aims:</b> To determine the safety of first-line tyrosine kinase inhibitors (TKIs) in advanced hepatocellular carcinoma (HCC) treatment by assessing the adverse drug reactions (ADRs) as reported in the World Health Organization (WHO)-VigiAccess database. <b>Methods:</b> We compiled ADR reports for two first-line TKIs from WHO-VigiAccess with retrospective descriptive analysis, gathering data on the disease systems and symptoms associated with ADRs, as well as population and geographic characteristics of advanced HCC patients. <b>Results:</b> A total of 63,375 ADR reports were analyzed for two first-line TKIs used in advanced HCC treatment: lenvatinib (<i>N</i> = 28,419) and sorafenib (<i>N</i> = 34,956). Gender distribution revealed male predominance for sorafenib (67.62%), whereas lenvatinib had more female reporters (53.40%). Among the 27 system organ classes, gastrointestinal disorders had the highest number of ADR reports for lenvatinib (15,683, 55.18%) and sorafenib (21,423, 61.29%). Based on gastrointestinal disorders, lenvatinib and sorafenib had similar reporting odds ratio (ROR) of 0.94 (0.96-0.92) and 0.96 (0.98-0.94) and proportional reporting ratio (PRR) of 0.95 (0.97-0.94) and 0.97 (0.98-0.95). The highest proportions of adverse reactions of diarrhea reported for the two drugs were 12% for lenvatinib and 15.74% for sorafenib. <b>Conclusion:</b> While gastrointestinal toxicities were class-wide concerns, agent-specific risks necessitate tailored monitoring. These findings emphasized the need for vigilant monitoring and personalized management in clinical practice.