Management of hypertension during lenvatinib for advanced thyroid cancer: a suggested diagnostic and therapeutic algorithm

Abstract

Background: Hypertension (HTN) is the most frequent adverse event during treatment with Lenvatinib (LEN), but data on its best management are limited. Aim: To assess incidence, features and best management of LEN-related HTN in a consecutive single tertiary-care Centre cohort. Methods: 29 patients followed for a mean time of 29.8 months (6-77 months). Results: After a mean follow-up of 6.8 months, HTN was recorded in 76% of cases, as a de novo occurrence in half of them. HTN significantly correlated with LEN dose, and was of grade 1, grade 2 and grade 3 in 5%, 50% and 45% of patients, respectively. The majority (77%) of patients with HTN developed proteinuria. There was no correlation between HTN and either proteinuria or clinical features or best morphological response or any other AE, with the exception of diarrhoea. Patients with or without pre-existing HTN or any other cardiovascular disease had a similar incidence of HTN during LEN, thus excluding the impact of this potential predisposing factor. After evaluation by a dedicated cardiologist, medical treatment was introduced in 21/22 patients (polytherapy in 20 of them). The most frequently used drugs were calcium channel blockers (CCB) due to their effect on vasodilation. In case of poor control, CCB were associated with one or more anti-hypertensive drug. Conclusion: HTN is a frequent and early adverse event in patients on LEN treatment. We suggest a diagnostic-therapeutic algorithm to be applied in clinical practice to allow efficient HTN control and improve patient compliance, reducing LEN discontinuation.

Association between baseline blood pressure and the incidence of lenvatinib‐induced hypertension in patients with thyroid cancer

“…Interestingly, in a recent cohort study evaluating a series of patients treated with doses ranging from 4 to 24 mg/day, the incidence and grade of hypertension were positively correlated with the lenvatinib dosage. 24 Similarly, higher plasma concentrations of lenvatinib have been reported to be associated with a higher incidence of severe hypertension. 25 Thus, blood pressure should be carefully monitored during lenvatinib administration because of the highest dose of 24 mg/day for thyroid cancer.…”

“…In addition, with regards to the ΔSBP and ΔDBP trends, the maximum value during the treatment period was observed 3 days after the start of treatment in the HTN group. Interestingly, in a recent cohort study evaluating a series of patients treated with doses ranging from 4 to 24 mg/day, the incidence and grade of hypertension were positively correlated with the lenvatinib dosage 24 . Similarly, higher plasma concentrations of lenvatinib have been reported to be associated with a higher incidence of severe hypertension 25 .…”

“…In the present study, 78% of patients who received antihypertensive intervention after starting lenvatinib received a combination of ACEI/ARB and CCB, and no patient had to discontinue lenvatinib due to poorly controlled hypertension. In a recent retrospective cohort study of 29 patients treated with lenvatinib, 95% of patients who were treated with antihypertensive drugs received two or more antihypertensive agents in combination to control blood pressure 24 . Therefore, after initiation of lenvatinib, early treatment with antihypertensive drugs, including combination drugs, may be useful for good blood pressure control.…”

“…In a recent retrospective cohort study of 29 patients treated with lenvatinib, 95% of patients who were treated with antihypertensive drugs received two or more antihypertensive agents in combination to control blood pressure. 24 Therefore, after initiation of lenvatinib, early treatment with antihypertensive drugs, including combination drugs, may be useful for good blood pressure control.…”