Safety evaluation of tucatinib: Adverse event signal mining and analysis based on the FAERS database

The purpose of this study was to evaluate the adverse events (AEs) associated with tucatinib by mining data from the U.S. Food and Drug Administration Adverse Event Reporting System (FAERS) and explore potential drug-related AEs, thereby guiding safe clinical use. We extracted AE reports involving tucatinib from the FAERS database spanning from the 1st quarter of 2020 to the 4th quarter of 2024. The reports were categorized based on preferred terms and system organ classes, and risk signals were subsequently grouped for further analysis. Among 12,225 AEs listing tucatinib as the primary suspected drug, a total of 103 preferred terms for AEs were identified across 22 different system organ classes. In these reports, the proportion of females was higher than males (97.02% vs 1.26%), and the highest number of AEs was reported in the 45 to 59 years (15.29%). The median (interquartile range) time to AE onset was 30.00 days (8.00-104.00). And the most of AEs occurred mainly within the 1st month (n = 152, 26.16%) or >60 days after drug administration (n = 106, 18.24%). Among the numerous positive risk signals, such as diarrhea, nausea, vomiting, stomatitis, rash, palmar-plantar erythrodysesthesia syndrome, hepatotoxicity, anemia, and peripheral neuropathy exhibited high signal strength, which largely aligned with the current prescribing information. In addition, some AEs not explicitly mentioned in the package insert were also observed. These included platelet count abnormal, ejection fraction decreased, aortic valve incompetence, dehydration, hypokalemia, and various nail or skin-related problems (e.g., fingerprint loss, ingrowing nail, onychalgia, onychomadesis, skin discoloration/hypertrophy/hyperpigmentation/exfoliation, pigmentation disorder, blister, etc), as well as nervous system disorders (e.g., memory impairment, brain edema, central nervous system lesion, hyperesthesia, taste disorder, emotional disorder) and paronychia. There is also a risk of various AEs in the treatment of tucatinib. In clinical application, it is so essential to monitor closely the dermatologic/nail conditions, gastrointestinal issues, cardiovascular abnormalities, and neuropsychiatric manifestations. Should any adverse events occur or disease progression be observed, timely intervention is necessary to prevent severe organ damage and further disease deterioration.