Early Increases in Blood Pressure and Major Adverse Cardiovascular Events in Patients With Renal Cell Carcinoma and Thyroid Cancer Treated With VEGFR TKIs
Abramson Cancer Center, University of Pennsylvania, Philadelphia, Pennsylvania
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Abramson Cancer Center, University of Pennsylvania, Philadelphia, Pennsylvania
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Abramson Cancer Center, University of Pennsylvania, Philadelphia, Pennsylvania
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Division of Cardiovascular Medicine, Department of Medicine, University of Pennsylvania, Philadelphia, Pennsylvania
Department of Biostatistics, Epidemiology & Informatics, Perelman School of Medicine at the University of Pennsylvania, Philadelphia, Pennsylvania
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Background: Although VEGFR tyrosine kinase inhibitors (TKIs) are a preferred systemic treatment approach for patients with advanced renal cell carcinoma (RCC) and thyroid carcinoma (TC), treatment-related cardiovascular (CV) toxicity is an important contributor to morbidity. However, the clinical risk assessment and impact of CV toxicities, including early significant hypertension, among real-world advanced cancer populations receiving VEGFR TKI therapies remain understudied. Methods: In a multicenter, retrospective cohort study across 3 large and diverse US health systems, we characterized baseline hypertension and CV comorbidity in patients with RCC and those with TC who are newly initiating VEGFR TKI therapy. We also evaluated baseline patient-, treatment-, and disease-related factors associated with the risk for treatment-related early hypertension (within 6 weeks of TKI initiation) and major adverse CV events (MACE), accounting for the competing risk of death in an advanced cancer population, after VEGFR TKI initiation. Results: Between 2008 and 2020, 987 patients (80.3% with RCC, 19.7% with TC) initiated VEGFR TKI therapy. The baseline prevalence of hypertension was high (61.5% and 53.6% in patients with RCC and TC, respectively). Adverse CV events, including heart failure and cerebrovascular accident, were common (occurring in 14.9% of patients) and frequently occurred early (46.3% occurred within 1 year of VEGFR TKI initiation). Baseline hypertension and Black race were the primary clinical factors associated with increased acute hypertensive risk within 6 weeks of VEGFR TKI initiation. However, early significant “on-treatment” hypertension was not associated with MACE. Conclusions: These multicenter, real-world findings indicate that hypertensive and CV morbidities are highly prevalent among patients initiating VEGFR TKI therapies, and baseline hypertension and Black race represent the primary clinical factors associated with VEGFR TKI–related early significant hypertension. However, early on-treatment hypertension was not associated with MACE, and cancer-specific CV risk algorithms may be warranted for patients initiating VEGFR TKIs.
Submitted December 22, 2022; final revision received June 16, 2023; accepted for publication June 19, 2023.
Previous presentation: This article was accepted for presentation at the American College of Cardiology 2023 Annual Scientific Session & Expo; March 4–6, 2023; New Orleans, Louisiana.
Author contributions: Concept and design: Narayan, Liu, Song, Mitchell, Sicks, Gareen, Sun, Margulies, Ky. Provision of study data: Narayan, Mitchell, Sun, Denduluri, Fisher, Manikowski, Wojtowicz, Vadakara, Haas, Margulies, Ky. Data analyses: Narayan, Liu, Song, Mitchell, Sicks, Gareen, Sun, Margulies, Ky. Manuscript writing: Narayan, Liu, Song, Mitchell, Margulies, Ky. Manuscript revision: Narayan, Liu, Song, Mitchell, Sicks, Gareen, Haas, Margulies, Ky.
Disclosures: The authors have disclosed that they have not received any financial consideration from any person or organization to support the preparation, analysis, results, or discussion of this article.
Funding: Research reported in this publication was supported by the National Heart, Lung, and Blood Institute of the National Institutes of Health under award number 5-R34-HL-146927-02 (B. Ky, K.B. Margulies) and National Cancer Institute grant UGI CA 189828-01 (B. Ky).
Disclaimer: The content is solely the responsibility of the authors and does not necessarily represent the official views of the National Institutes of Health.
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