A Real-World Disproportionality Analysis of Two Typical First-Generation
TRK Inhibitors: Findings from the FDA Adverse Event Reporting System
Database
Abstract
Background: Although Two first-generation tropomyosin receptor kinase
(TRK) inhibitors larotrectinib and entrectinib have been approved by the
Food and Drug Administration (FDA), The current adverse effect profile
in the real world remains unknown. Objective: The purpose of this study
was to retrospectively examine the adverse effects of two typical
first-generation TRK inhibitors by spontaneously mining the data from
FDA Adverse Event Reporting System (FAERS) database. Methods: Four
general data mining algorithms were used to conduct a disproportionate
analysis of TRK inhibitors, and the time of adverse events of drugs was
counted. The definition relied on the system organ class (SOC) and
preferred terms (PT) by the MedDRA. Results: A total of 326 cases of
‘larotrectinib’ and 450 cases of ‘entrectinib’ as the ‘primary suspect’
drug were collected in this study. A total of 86 adverse drug reaction
(ADR) signals involving 18 SOCs were mined. ‘Dizziness’ was the most
common ADR, with ‘glioma’ as the strongest signal. The SOC with the
highest number of occurrences was ‘Nervous system disorders’.The median
time of onset of larotinib and entertinib-related ADR was 41 days and 18
days, respectively. Most cases occurred within one month after
treatment. Conclusion: The main ADRs found in this study were
‘Neurotoxicity’, ‘Pain’, ‘Hepatotoxicity’, ‘Drug resistance’,
‘Nephrotoxicity’ and ‘Weight increased’, which provide important support
for clinical monitoring and risk identification of TRK inhibitors.