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

Wendy J. Bottinor, Yael Flamand, Naomi B. Haas, Anne M. ONeill, Robert S. DiPaola, Pearl Subramanian, David Cella, W. Gregory Hundley, Lynne I. Wagner, John M. Salsman, Bonnie Ky

Research output: Contribution to journalArticlepeer-review


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 fromthe ASSURE trial ( 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.

Original languageEnglish
Pages (from-to)725-731E1
JournalJNCCN Journal of the National Comprehensive Cancer Network
Issue number7
StatePublished - Jul 2023

Bibliographical note

Funding Information:
Funding: Research reported in this publication was supported by ECOG-ACRIN (award number UG1CA189828-06-VCU1). This study was conducted by the ECOG-ACRIN Cancer Research Group (Peter J. O’Dwyer, MD, and Mitchell D. Schnall, MD, PhD, Group Co-Chairs) and supported by the National Cancer Institute of the National Institutes of Health under award numbers U10CA180820, U10CA180794, UG1CA189828, UG1CA233270, UG1CA233196, UG1CA233320, and UG1CA189869. The research reported in this publication was also supported by CTSA award No. KL2TR002648 from the National Center for Advancing Translational Sciences, Tomorrow’s Research Fund St. Baldrick’s Scholar Award (award number 636214), and American Heart Association (award number 19CDA34760181).

Publisher Copyright:
© 2023 Harborside Press. All rights reserved.

ASJC Scopus subject areas

  • Oncology


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