Anlotinib-Induced Hypertension: Current Concepts and Future Prospects

Anlotinib is a new tyrosine kinase inhibitor developed in China that targets the receptors for vascular endothelial growth factor, platelet-derived growth factor, fibroblast growth factor, and stem cell factor. Therefore, anlotinib inhibits tumor angiogenesis, representing a new therapeutic alternative for lung cancer. Hypertension is one of its most common adverse effects, leading to discontinuation of the drug and limited clinical usefulness.

The present review aims to summarize the evidence on the prevalence, physiopathology, and management of anlotinib-induced hypertension, as well as its effect on the cancer prognosis.

Searches in Medline, Cochrane Central Library, and Embase were performed using the following terms: anlotinib, adverse effect, hypertension, clinical trial, vascular endothelial growth factor, and anti-angiogenic drugs. Citations were also identified by checking the reference sections of selected papers.

Except for a phase I clinical trial with a small sample size (n = 6), almost all the clinical trials on anlotinib have reported the development of anlotinib-induced hypertension. In these trials, the incidence of hypertension ranged from 13% to 67.7%, and that of grade 3/4 hypertension ranged from 4.8% to 16%. Alterations in nitric oxide, endothelin-1, microvascular rarefaction, selective vasoconstrictions, and renal injury have been cited as potential mechanisms leading to anlotinib-induced hypertension. When needed, treatment may include general hygienic measures and pharmacotherapy in some cases.

To effectively manage anlotinib-induced hypertension, early prevention, a reasonable dosage regimen, and appropriate treatment are critical to effectively manage anlotinib-induced hypertension. Additionally, anlotinib-induced hypertension may be considered a marker for predicting efficacy.