Hypertension and VEGF-A level correlation in cancer patients starting VEGF inhibitors: A prospective study.

Abstract

e16543 Background: Vascular endothelial growth factor inhibitors (VEGFi) are commonly used in cancer therapy. VEGFi can cause hypertension by interference with nitric oxide-mediated vasodilation. The incidence of hypertension from VEGFi varies due to different definitions in clinical trials. Understanding the timeline and predictors of hypertension onset could improve patient management. Methods: This single-center prospective cohort study includes patients without diabetes, hypertension, or proteinuria scheduled for systemic VEGFi treatment. Serum VEGF-A and 24-hour urine proteinuria were measured at baseline, week 4, and week 12. Weekly home blood pressure (BP) was assessed weekly at baseline, week 1, 4, 8, and 12. Results: Fifty-five patients (median age was 59 years (49.5-66), M:F 1.6:1) were included in this study between January 1, 2021, and July 31, 2022. Most had kidney cancer (42, 76%), while others include ovary (n=5), neuroendocrine tumor (n=2), sarcoma (n=3), thyroid (n=3), liver (n=1), and colon (n=1). VEGFi used were Sunitinib (n=21), Lenvatinib (n=14), Cabozantinib (n=8), Bevacizumab (n=5), Axitinib (n=4), and Pazopanib (n=3). During follow-up, 2 patients died, and 1 patient did not report home BP. By week 1, thirty-nine (70.9%) patients developed grade 2 HTN (BP 140-159/90-99 mm Hg), increasing to 52 (94.5%) by week 4. The median systolic BP (SBP), diastolic BP (DBP), VEGF-A, and 24-hour urine protein significantly increase from baseline to week 12 (p < 0.001). DBP at week 1 correlated positively with VEGF-A level at week 4 (p=0.009, rho=0.35) and VEGF-A level at week 12 (p=0.001, rho=0.44). Proteinuria of 500 mg/day occurred in 31% at week 4 and 45% by week 12, but no nephrotic range proteinuria was observed. There was no correlation between 24-hour protein and DBP or SBP levels. No correlation was found between 24-hour protein levels and VEGF-A levels. Conclusions: Approximately 70% of patients developed grade 2 HTN within one week of starting VEGFi, and about half had onset of sub-nephrotic proteinuria by week 12. VEGF-A levels after treatment correlated positively with diastolic BP at week 1. This highlights the importance of early monitoring of HTN and proteinuria. Further studies should examine predictors of HTN development, including biomarkers after VEGFi such as VEGF-A levels, in a larger population with longer follow-up. Demographic characteristics and results at baseline, 4 and 12 weeks. Parameter Median(Range) Baseline 1 week week 2 week 4 week 8 week 12 p value SBP in mmHg 122 (110-133) 140 (100-188) 142 (117-200) 145 (110-198) 145 (110-198) 145 (121-250) <0.001 DBP in mmHg 75 (60-90) 90 (55-104) 90 (67-110) 90 (75-108) 90 (60-105) 90 (70-120) <0.001 Proteinuria mg/d 140 (102-256) 400 (180-523) 480 (120-1200) <0.001 SerumVEGF-A(pg/mL) 304 (172-650) 340 (181-522) 384 (184-570) <0.001 Creatinine (mg/dL) 0.9 (0.2-1.5) 0.9 (0.2-2.6) 0.9 (0.3-2.3) 0.58