Posterior Reversible Encephalopathy Syndrome with Angiogenesis Inhibitors for Solid Tumours: Clues from a...

Posterior reversible encephalopathy syndrome (PRES) is a rare neurologic condition that may occur as an adverse drug reaction (ADR).

We aimed to characterize post-marketing reporting of PRES related to angiogenesis inhibitors targeting the vascular endothelial growth factor and its receptor (VEGF/VEGFR) and to explore the underlying pharmacodynamic mechanisms.

A disproportionality analysis was performed within the FDA Adverse Event Reporting System (FAERS) database. The Bayesian information component (IC) was calculated to detect signals of disproportionate reporting (SDRs), with subgroup analyses by treatment regimen, and coreported drugs as proxies for risk factors of PRES. A network analysis identified clusters of coreported events, and univariate regression models that interpolated disproportionality and receptor affinities (extracted from ChEMBL and IUPHAR/BPS databases) were performed.

We found 856 reports of PRES associated with anti-VEGF therapies (88.5% by healthcare professionals; 49% by tyrosine kinase inhibitors; 48% by monoclonal antibodies; 72% with immunotherapy in the 2021-2024 period). Patients were mainly females (68%), with a median age of 62 years (IQR 52-69). SDRs emerged for 12 drugs, notably bevacizumab [N = 393; IC = 3.17; 95% confidence interval (CI) 3.00-3.29] and lenvatinib (132; 3.27; 2.98-3.48). Hypertension, headache, confusional state, and proteinuria emerged in a coreported syndromic cluster. Only fibroblast growth factor receptor (FGFR) 4 emerged with a significant inverse association (β = - 0.107, p = 0.001).

Although causality cannot be established, these findings raise the hypothesis that PRES could be a class effect of angiogenesis inhibitors and call for ongoing epidemiological surveillance and timely multiprofessional management of hypertension as a risk-minimization strategy. The potential modulatory role of FGFR4 deserves further mechanistic translational studies.