Cardiovascular toxicities associated with vascular endothelial growth factor receptor tyrosine kinase inhibitors: a pharmacovigilance study based on FDA adverse event reporting system.

Abstract

Background: Vascular endothelial growth factor receptor (VEGFR) tyrosine kinase inhibitors (TKIs) are widely used in the treatment of various cancers. However, post-marketing evidence regarding their cardiovascular toxicities remains limited.

Aim: This pharmacovigilance study aimed to comprehensively evaluate the association between VEGFR-TKIs and cardiovascular toxicities in cancer patients.

Method: We retrieved and analyzed cardiovascular toxicity reports related to VEGFR-TKIs from the FDA Adverse Event Reporting System (FAERS). Disproportionality analyses were performed using the proportional reporting ratio (PRR), reporting odds ratio (ROR), information component (IC), and empirical Bayes geometric mean (EBGM) to detect safety signals of cardiovascular toxicities associated with VEGFR-TKIs.

Results: A total of 12,726 cancer patients experienced cardiovascular toxicities associated with VEGFR-TKI treatment. All eleven VEGFR-TKIs were associated with cardiovascular toxicities, with hypertension being the most consistently reported event across all agents. Among them, cabozantinib was associated with the highest number of cardiovascular events, whereas lenvatinib exhibited the strongest signal. Notably, lenvatinib was associated with cardiac failure (ROR = 2.521, PRR = 2.479, IC = 1.308, EBGM = 2.476) and cardiomyopathy (ROR = 2.801, PRR = 2.788, IC = 1.476, EBGM = 2.782); sunitinib with cardiac failure (ROR = 2.745, PRR = 2.693, IC = 1.426, EBGM = 2.687) and cardiomyopathy (ROR = 3.020, PRR = 3.004, IC = 1.584, EBGM = 2.997); ponatinib with cardiomyopathy (ROR = 3.393, PRR = 3.372, IC = 1.752, EBGM = 3.368); and vandetanib with Torsade de pointes/QT prolongation (ROR = 27.930, PRR = 26.101, IC = 4.703, EBGM = 26.051).

Conclusion: VEGFR-TKIs were associated with cardiovascular toxicities, particularly hypertension. Notably, lenvatinib and sunitinib were associated with cardiac failure and cardiomyopathy, ponatinib with cardiomyopathy, and vandetanib with Torsade de pointes and QT prolongation. Future prospective studies are warranted to further clarify the causal relationships between these agents and cardiovascular toxicities.