Cardiovascular Implications of Vascular Endothelial Growth Factor Inhibition Among Adolescents/Young Adults in ECOG-ACRIN E2805

Abstract

Background: Cardiovascular disease (CVD) is a leading cause of morbidity and mortality among adolescents and young adults (AYAs) diagnosed with cancer. The aim of this study was to assess the incidence and predictors of left ventricular systolic dysfunction (LVSD) and hypertension among AYAs receiving VEGF inhibition compared with non-AYAs. Methods: This retrospective analysis used data from the ASSURE trial (ClinicalTrials.gov identifier: NCT00326898), in which participants with nonmetastatic, high-risk, renal cell cancer were randomized to sunitinib, sorafenib, or placebo. The incidence of LVSD (left ventricular ejection fraction decrease >15%) and hypertension (blood pressure ≥140/90 mm Hg) were compared using nonparametric tests. Multivariable logistic regression examined the association between AYA status, LVSD, and hypertension while adjusting for clinical factors. Results: AYAs represented 7% (103/1,572) of the population. Over a study treatment period of 54 weeks, the incidence of LVSD was not significantly different among AYAs (3%; 95% CI, 0.6%–8.3%) versus non-AYAs (2%; 95% CI, 1.2%–2.7%). The incidence of hypertension was significantly lower among AYAs (18%; 95% CI, 7.5%–33.5%) compared with non-AYAs (46%; 95% CI, 41.9%–50.4%) in the placebo arm. In the sunitinib and sorafenib groups, the incidence of hypertension for AYAs compared with non-AYAs was 29% (95% CI, 15.1%–47.5%) versus 47% (95% CI, 42.3%–51.7%), and 54% (95% CI, 33.9%–72.5%) versus 63% (95% CI, 58.6%–67.7%), respectively. AYA status (odds ratio, 0.48; 95% CI, 0.31–0.75) and female sex (odds ratio, 0.74; 95% CI, 0.59–0.92) were each associated with a lower risk of hypertension. Conclusions: LVSD and hypertension were prevalent among AYAs. CVD among AYAs is only partially explained by cancer therapy. Understanding CVD risk among AYA cancer survivors is important for promoting cardiovascular health in this growing population.

Vascular Endothelial Growth Factor (VEGF) and Its Role in the Cardiovascular System

“…ASSURE trial [80] sunitinib or sorafenib sunitinib sorafenib Sunitinib was associated with a significantly lower incidence of hypertension than sorafenib.…”

“…There are not enough data from clinical trials focusing on the influence of anti-VEGF treatment on cardiovascular adverse events. The only medications considered in the clinical trials were brolicizumab, sunitinib, and sorafenib, as well as cediranib in combination with selumetinib [79][80][81]. Brolicizumab intravitreal injections in neovascular age-related macular degeneration (nAMD) did not significantly influence cardiac pathologies.…”

“…The results showed that sunitinib was associated with a significantly lower incidence of hypertension as compared to sorafenib. Additionally, hypertension after treatment with those medications was less common among the AYA than non-AYA group [80]. Moreover, results from a phase I trial on cediranib in combination with selumetinib use in solid tumors showed that continuous therapy was not well-tolerated in terms of cardiovascular toxicities.…”