Treatment and Implications of Vascular Endothelial Growth Factor Inhibitor-Induced Blood Pressure Rise: A Clinical Cohort Study

BACKGROUND: Anti-cancer vascular endothelial growth factor inhibitors (VEGFI) frequently induce a rise in blood pressure (BP). The most effective treatment of this BP rise is currently unknown, and risk factors and its association with survival remain inconclusive. METHODS AND RESULTS: Baseline characteristics and BP readings were retrospectively collected from oncology patients who received oral VEGFI treatment (sorafenib, sunitinib, pazopanib, regorafenib, lenvatinib, or cabozantinib). Risk factors for a clinically relevant BP rise (increase of ≥20 mm Hg in systolic BP or ≥10 mm Hg in diastolic BP) were investigated via logistic regression (relative), efficacy of antihypertensives via unpaired t-tests, and association of BP rise with survival via Cox regression analysis. In total, 162 (47%) of 343 included patients developed a clinically relevant BP rise ≥7 days after VEGFI treatment initiation. Both calcium channel blockers and renin-angiotensin system inhibitors effectively reduced systolic BP (−24.1 and −18.2 mm Hg, respectively) and diastolic BP (−12.0 and −11.0 mm Hg, respectively). Pazopanib therapy (odds ratio, 2.71 [95% CI, 1.35– 5.42; P=0.005], compared with sorafenib) and estimated glomerular filtration rate <60 mL/min per 1.73 m² (OR, 1.75 [95% CI, 0.99– 3.18, P=0.054]) were risk factors for a BP rise, whereas a baseline BP ≥140/90 mm Hg associated with a lower risk (OR, 0.39 [95% CI, 0.25– 0.62, P<0.001]). Only for renal cell carcinoma, BP rise was associated with a substantially improved median overall survival compared with no BP rise: 45.4 versus 20.3 months, respectively, P=0.003. CONCLUSIONS: The type of VEGFI, baseline BP, and baseline estimated glomerular filtration rate determine the VEGFI-induced BP rise. Both calcium channel blockers and renin-angiotensin system inhibitors are effective antihypertensive treatments. Particularly in patients with renal cell carcinoma, a BP rise is associated with improved overall survival.