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Hypertension occurred in 73% of patients in SELECT (DTC) receiving lenvatinib 24 mg orally once daily and in 45% of patients in REFLECT (HCC) receiving lenvatinib 8 mg or 12 mg orally once daily. The median time to onset of new or worsening hypertension was 16 days in SELECT and 26 days in REFLECT. Grade 3 hypertension occurred in 44% of patients in SELECT and in 24% in REFLECT. Grade 4 hypertension occurred <1% in SELECT and Grade 4 hypertension was not reported in REFLECT.
In patients receiving lenvatinib 18 mg orally once daily with everolimus in Study 205 (RCC), hypertension was reported in 42% of patients and the median time to onset of new or worsening hypertension was 35 days. Grade 3 hypertension occurred in 13% of patients. Systolic blood pressure ≥160 mmHg occurred in 29% of patients and diastolic blood pressure ≥100 mmHg occurred in 21%.
Serious complications of poorly controlled hypertension have been reported.
Control blood pressure prior to initiating lenvatinib. Monitor blood pressure after 1 week, then every 2 weeks for the first 2 months, and then at least monthly thereafter during treatment. Withhold and resume at a reduced dose when hypertension is controlled or permanently discontinue lenvatinib based on severity.
Serious and fatal cardiac dysfunction can occur with lenvatinib. Across clinical trials in 799 patients with DTC, RCC or HCC, Grade 3 or higher cardiac dysfunction (including cardiomyopathy, left or right ventricular dysfunction, congestive heart failure, cardiac failure, ventricular hypokinesia, or decrease in left or right ventricular ejection fraction of more than 20% from baseline) occurred in 3% of lenvatinib-treated patients.
Monitor patients for clinical symptoms or signs of cardiac dysfunction. Withhold and resume at a reduced dose upon recovery or permanently discontinue lenvatinib based on severity.
Among patients receiving lenvatinib or lenvatinib with everolimus, arterial thromboembolic events of any severity occurred in 2% of patients in Study 205 (RCC), 2% of patients in REFLECT (HCC) and 5% of patients in SELECT (DTC). Grade 3 to 5 arterial thromboembolic events ranged from 2% to 3% across all clinical trials.
Among patients receiving lenvatinib with pembrolizumab, arterial thrombotic events of any severity occurred in 5% of patients in CLEAR, including myocardial infarction (3.4%) and cerebrovascular accident (2.3%).
Permanently discontinue lenvatinib following an arterial thrombotic event. The safety of resuming lenvatinib after an arterial thromboembolic event has not been established and lenvatinib has not been studied in patients who have had an arterial thromboembolic event within the previous 6 months.
Monitor liver function prior to initiating lenvatinib, then every 2 weeks for the first 2 months, and at least monthly thereafter during treatment. Monitor patients with HCC closely for signs of hepatic failure, including hepatic encephalopathy. Withhold and resume at a reduced dose upon recovery or permanently discontinue lenvatinib based on severity.
Initiate prompt management of diarrhea or dehydration/hypovolemia. Withhold and resume at a reduced dose upon recovery or permanently discontinue lenvatinib for renal failure or impairment based on severity.
from FDA，2024.06
