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

Abstract

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 m 2 (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.

2023 ESH Guidelines for the management of arterial hypertension The Task Force for the management of arterial hypertension of the European Society of Hypertension

“…In a retrospective cohort study involving 343 cancer patients that were treated with oral VEGF inhibitors (sorafenib, sunitinib, pazopanib, regorafenib, lenvatinib or cabozantinib), about half of the included patients exhibited significant BP increases (20 mmHg in SBP or 10 mmHg in DBP). Normotension at baseline and treatment with pazopanib identified as significant risk factors for this significant BP rise [1598]. Treatment with a CCB or RAS blocker (ACEi or ARB) effectively reduced SBP (24.1 and 18.2 mmHg, respectively) and DBP (12.0 and 11.0 mmHg, respectively) [1598].…”

“…Normotension at baseline and treatment with pazopanib identified as significant risk factors for this significant BP rise [1598]. Treatment with a CCB or RAS blocker (ACEi or ARB) effectively reduced SBP (24.1 and 18.2 mmHg, respectively) and DBP (12.0 and 11.0 mmHg, respectively) [1598]. In patients treated with VEGF inhibitors any BP-lowering therapy administered during the on-treatment periods must be carefully monitored, e.g.…”