Bevacizumab-induced hypertension and proteinuria: a genome-wide study of more than 1000 patients.
Publication/Presentation Date
2-1-2022
Abstract
BACKGROUND: Hypertension and proteinuria are common bevacizumab-induced toxicities. No validated biomarkers are available for identifying patients at risk of these toxicities.
METHODS: A genome-wide association study (GWAS) meta-analysis was performed in 1039 bevacizumab-treated patients of European ancestry in four clinical trials (CALGB 40502, 40503, 80303, 90401). Grade ≥2 hypertension and proteinuria were recorded (CTCAE v.3.0). Single-nucleotide polymorphism (SNP)-toxicity associations were determined using a cause-specific Cox model adjusting for age and sex.
RESULTS: The most significant SNP associated with hypertension with concordant effect in three out of the four studies (p-value < 0.05 for each study) was rs6770663 (A > G) in KCNAB1, with the G allele increasing the risk of hypertension (p-value = 4.16 × 10
CONCLUSIONS: The results from the largest study of bevacizumab toxicity provide new markers of drug safety for further evaluations. SNP in KCNAB1 validated in an independent dataset provides evidence toward its clinical applicability to predict bevacizumab-induced hypertension. ClinicalTrials.gov Identifier: NCT00785291 (CALGB 40502); NCT00601900 (CALGB 40503); NCT00088894 (CALGB 80303) and NCT00110214 (CALGB 90401).
Volume
126
Issue
2
First Page
265
Last Page
274
ISSN
1532-1827
Published In/Presented At
Quintanilha, J. C. F., Wang, J., Sibley, A. B., Jiang, C., Etheridge, A. S., Shen, F., Jiang, G., Mulkey, F., Patel, J. N., Hertz, D. L., Dees, E. C., McLeod, H. L., Bertagnolli, M., Rugo, H., Kindler, H. L., Kelly, W. K., Ratain, M. J., Kroetz, D. L., Owzar, K., Schneider, B. P., … Innocenti, F. (2022). Bevacizumab-induced hypertension and proteinuria: a genome-wide study of more than 1000 patients. British journal of cancer, 126(2), 265–274. https://doi.org/10.1038/s41416-021-01557-w
Disciplines
Business Administration, Management, and Operations | Health and Medical Administration | Management Sciences and Quantitative Methods
PubMedID
34616010
Department(s)
Administration and Leadership
Document Type
Article