A disproportionality analysis of adverse events caused by pexidartinib from the FDA adverse event reporting system

Area of Science:

• Oncology
• Pharmacovigilance
• Medical Informatics

Background:

• Tenosynovial giant cell tumor (TGCT) is a rare neoplasm linked to CSF1/CSF1R pathway dysregulation.
• High recurrence rates necessitate alternative treatments beyond surgery.
• Pexidartinib, a CSF1R inhibitor, is an explored therapeutic option.

Purpose of the Study:

• To analyze pexidartinib-associated adverse events (AEs) in TGCT patients.
• To identify potential sex-specific differences in AE profiles.
• To assess the robustness of AE signals using disproportionality and sensitivity analyses.

Main Methods:

• Retrospective pharmacovigilance study using FDA Adverse Event Reporting System (FAERS) data (Q4 2019-Q3 2024).
• Analysis of 844 pexidartinib-associated AE reports.
• Disproportionality analyses (ROR, PRR, BCPNN, EBGM) and sensitivity assessments were employed.

Main Results:

• Hepatic events (46.7% within 30 days) and systemic reactions (fatigue, hair discoloration) were common, with median onset at 35 days.
• Females (71.3% of cases) showed stronger signals for constipation and alopecia.
• 84 significant Preferred Terms were identified, with robust signals confirmed by sensitivity analyses.

Conclusions:

• Pexidartinib treatment for TGCT is associated with significant hepatotoxicity and delayed-onset AEs (18.2% after 6 months).
• Sex-dimorphic AE patterns necessitate tailored monitoring and risk management.
• FAERS data are valuable for post-marketing surveillance and optimizing the risk-benefit profile of pexidartinib.