Blood pressure elevations post-lenvatinib treatment in hepatocellular carcinoma: a potential marker for better prognosis

Lenvatinib is a tyrosine kinase inhibitor that effectively inhibits vascular endothelial growth factor signaling and is used for treating hepatocellular carcinoma. However, angiogenesis inhibitors often cause hypertension. Although lenvatinib-induced hypertension has been proposed as a potential surrogate marker for better prognosis, studies on blood pressure elevations and outcomes following lenvatinib initiation are limited. This study included 67 patients who underwent lenvatinib therapy at the Department of Gastroenterology, Kagoshima University Hospital, between May 2018 and December 2023. The median age of the cohort was 71 years, and 82.1% of the patients were male. The median blood pressure at admission was 128/73 mmHg, which significantly increased to 136/76 mmHg the day after lenvatinib administration. Grade 3 hypertension (≥160/100 mmHg) occurred in 37.3% of patients during hospitalization. The median increase in systolic blood pressure from admission to its peak during hospitalization was 26 mmHg. Patients who experienced an increase in blood pressure of ≥26 mmHg were classified into the blood pressure elevation group, which showed a significantly lower mortality rate than that of the blood pressure non-elevation group (35.3% vs. 81.8%, log-rank p = 0.007), even after adjusting for age, sex, disease stage, performance status, and liver reserve function. This study demonstrated that patients who experienced earlier blood pressure elevation after lenvatinib administration had lower overall mortality rates. These findings suggest that blood pressure elevations after lenvatinib initiation may serve as valuable prognostic indicators in patients with cancer undergoing lenvatinib therapy. • Early Blood Pressure Elevation Following Lenvatinib Administration Significant blood pressure elevation was observed from the day after Lenvatinib administration, with a median systolic blood pressure increase of 26 mmHg. Grade 3 hypertension (≥160/100 mmHg) was observed in 38% of patients during hospitalization. •Blood Pressure Control Antihypertensive therapy was intensified in 39% of patients during hospitalization, yet 12% still had Grade 3 hypertension the day before discharge. • Association Between Blood Pressure Elevation and Prognosis Even after adjusting for age, sex, disease stage, performance status, and liver function reserve, blood pressure elevation was suggested as a better prognostic factor.