Posterior Reversible Encephalopathy Syndrome (PRES) Associated With Lenvatinib: A Disproportionality Analysis

Background: Posterior reversible encephalopathy syndrome (PRES) is a rare but potentially life-threatening neurological condition characterized by seizures, headache, visual disturbances, and altered mental status, typically associated with vasogenic edema on neuroimaging. Although several anticancer therapies have been implicated in PRES, evidence regarding its association with lenvatinib remains limited. Purpose: The aim of this study was to investigate a potential safety signal between lenvatinib and PRES using a pharmacovigilance approach and evaluate whether reports of PRES are disproportionately associated with lenvatinib in a large spontaneous reporting database. Methods: A retrospective pharmacovigilance study was conducted using the FDA Adverse Event Reporting System (FAERS) database. Individual Case Safety Reports (ICSRs) mentioning lenvatinib and PRES were identified and extracted. Disproportionality analysis was performed by calculating the reporting odds ratio (ROR), proportional reporting ratio (PRR), and chi-square statistic. According to Evans' criteria (n > 2, PRR > 2, chi-square > 4), a drug-event combination is considered suggestive of a potential safety signal. Results: The disproportionality analysis revealed a statistically significant signal for PRES associated with lenvatinib. The PRR was 5.79 (95% CI: 4.80-6.98), and the ROR was 5.81 (95% CI: 4.81-7.00), both exceeding commonly accepted signal detection thresholds. These findings suggest that reports of PRES occur more frequently with lenvatinib than with other drugs in the database. Conclusion: This pharmacovigilance analysis identified a significant disproportionality signal suggesting a potential association between lenvatinib and PRES. Although spontaneous reporting systems cannot establish causality, these findings highlight the importance of clinical awareness and further investigation to better characterize this rare but serious adverse event.