The importance of early-stage blood pressure control in thyroid cancer patients treated with lenvatinib from the perspective of dose intensity

AbstractPurpose:Lenvatinib (LEN) is a multikinase inhibitor that strongly inhibits tyrosine kinase receptors, especially VEGFR-2, which can cause hypertension, as well as strong tumor shrinkage. Though control of any side effects (SEs) is important for maintaining dose intensity (DI), hypertension is particularly important, because blood pressure (BP) can change quickly and respond to LEN administration and withdrawal, and can be controlled with antihypertensive medications. Focusing on the early phase of treatment, the effect of BP 8 weeks after LEN initiation (BP8w) on DI at 8 weeks (DI8w) was investigated.Methods:The subjects were 85 thyroid cancer patients who started LEN at 24 mg/day and continued for ≥8 weeks. The BP at the start of LEN (BPbase), BP8wgrade, and DI8wwere examined.Results:Median (range) systolic BP changed significantly from BPbaseof 117 (84-167) mmHg to BP8wof 134 (103-168) mmHg (p<0.001). Antihypertensive treatment at baseline, systolic BPbase, and male sex were related to higher DI8won multivariate analysis. The median DI8wof the 23 patients who required dose modification due to hypertension was 20.2 mg/day (n=6) in grade 1, 15.8 mg/day (n=13) in grade 2, and 14.5 mg/day (n=4) in grade 3, showing a trend toward lower DI8was the grade level increased.Conclusion:LEN can increase BP by 20 mmHg at 8 weeks even with intensive antihypertensive management. Baseline antihypertensive treatment and BPbasecan affect DI8w. A higher DI8wmay be achieved by aiming for a low 8-week BP with more intensive antihypertensive care after LEN initiation.