Investigating Drug-Induced Thyroid Dysfunction Adverse Events Associated With Non-Selective RET Multi-Kinase...

Area of Science:

• Pharmacovigilance and Drug Safety
• Oncology and Endocrinology
• Clinical Pharmacology

Background:

• Thyroid dysfunction (TD) is a potential adverse event associated with targeted cancer therapies.
• Non-selective RET kinase inhibitors (MKIs) are increasingly used in cancer treatment, necessitating an understanding of their safety profile.
• The association between non-selective MKIs and TD requires thorough investigation.

Purpose of the Study:

• To investigate the potential association between non-selective RET kinase inhibitors and thyroid dysfunction (TD).
• To conduct a pharmacovigilance analysis using US FDA Adverse Event Reporting System (FAERS) data.
• To identify specific TD adverse events and influencing factors associated with non-selective MKI use.

Main Methods:

• Utilized FAERS data from Q1 2015 to Q4 2023 for non-selective RET MKIs.
• Employed disproportionality analysis (ROR, PRR, BCPNN, EBGM) to detect AE signals for TD.
• Conducted subgroup analyses, multivariate logistic regressions, and time-to-onset (TTO) analysis.

Main Results:

• A descriptive analysis showed an increasing trend in TD adverse events with non-selective RET MKIs, including serious reactions.
• Disproportionality analyses consistently indicated a positive association between Sunitinib, Cabozantinib, and Lenvatinib with TD.
• Subgroup and logistic regression analyses identified age, gender, and weight as significant factors influencing TD occurrence, with early TTO observed.

Conclusions:

• The study indicates a correlation between non-selective RET MKIs and TD adverse events.
• Findings support enhanced clinical monitoring and risk identification for patients on these inhibitors.
• Further clinical studies are recommended to validate these pharmacovigilance findings.