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Contribution of plasma levels of VEGF-A and angiopoietin-2 in addition to a genetic variant in KCNAB1 to predict the risk of bevacizumab-induced hypertension

The Pharmacogenomics Journal volume 24, Article number: 22 (2024) Cite this article

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Abstract

Bevacizumab-induced hypertension poses a therapeutic challenge and identifying biomarkers for hypertension can enhance therapy safety. Lower plasma levels of VEGF-A, angiopoietin-2, and rs6770663 in KCNAB1 were previously associated with increased risk of bevacizumab-induced hypertension. This study investigated whether these factors independently contribute to grade 2–3 bevacizumab-induced hypertension risk in 277 cancer patients (CALGB/Alliance 90401). Multivariable analyses assessed the independent association of each factor and hypertension. Likelihood ratio test (LRT) evaluated the explanatory significance of combining protein levels and rs6770663 in predicting hypertension. Boostrap was employed to assess the mediation effect of protein levels on the rs6770663 association with hypertension. Lower protein levels and rs6770663 were independently associated with increased hypertension risk. Adding rs6770663 to protein levels improved the prediction of hypertension (LRT p = 0.0002), with no mediation effect observed. Protein levels of VEGF-A, angiopoietin-2 and rs6770663 in KCNAB1 are independent risk factors and, when combined, may improve prediction of bevacizumab-induced hypertension. ClinicalTrials.gov Identifier: NCT00110214.

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Data availability

The datasets generated during and/or analysed during the current study are available from the corresponding author on reasonable request.

Code availability

Code used for the analyses of the current study are available from the corresponding author on reasonable request.

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Acknowledgements

Research reported in this publication was supported by the National Cancer Institute of the National Institutes of Health under Award Numbers U10CA180821 and U10CA180882 (to the Alliance for Clinical Trials in Oncology), UG1CA233373. Also supported in part by funds from Genentech. 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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Authors and Affiliations

  1. University of North Carolina Eshelman School of Pharmacy, University of North Carolina at Chapel Hill, Chapel Hill, NC, US

    Julia C. F. Quintanilha & Federico Innocenti

  2. Sidney Kimmel Cancer Center, Thomas Jefferson University Hospital, Philadelphia, PA, US

    William Kevin Kelly

Authors
  1. Julia C. F. Quintanilha
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  2. William Kevin Kelly
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  3. Federico Innocenti
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Contributions

JCFQ contributed to formal analysis, methodology, investigation and writing – original draft, review and editing. WKK contributed to funding acquisition and writing – original draft, review and editing. FI contributed to conceptualization, funding acquisition, formal analysis, investigation, methodology, supervision, and writing – original draft, review, and editing.

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Correspondence to Julia C. F. Quintanilha.

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Competing interests

JCFQ is an employee of Foundation Medicine, a wholly owned subsidiary of Roche, and receives stocks from Roche. FI is an employee of AbbVie and receives stocks from the company. JCFQ and FI are coinventors of a United States Patent: “Methods of identifying risk of bevacizumab-induced proteinuria and hypertension”, FI, JCFQ., Lin D., Owzar K., Wang J. Serial number 11,028,448. WKK, DO- no conflicts of interest.

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Quintanilha, J.C.F., Kelly, W.K. & Innocenti, F. Contribution of plasma levels of VEGF-A and angiopoietin-2 in addition to a genetic variant in KCNAB1 to predict the risk of bevacizumab-induced hypertension. Pharmacogenomics J 24, 22 (2024). https://doi.org/10.1038/s41397-024-00342-1

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  • DOI: https://doi.org/10.1038/s41397-024-00342-1

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