Plasma levels of angiopoietin-2, VEGF-A, and VCAM-1 as markers of bevacizumab-induced hypertension: CALGB 80303 and 90401 (Alliance)

Plasma levels of VEGF‐A and VCAM‐1 as predictors of drug‐induced hypertension in patients treated with VEGF pathway inhibitors

“…This study aimed to validate the association between plasma levels of proteins involved in the function of the vasculature and hypertension induced by VEGF pathway inhibitors. Our previous study 11 reported that lower levels of angiopoietin‐2, VCAM‐1 and VEGF‐A are associated with bevacizumab‐induced hypertension. This current study has validated the association between lower levels of VCAM‐1 and VEGF‐A and regorafenib‐induced hypertension.…”

“…All assays were performed with coefficients of variation (CVs) ranging from 1.4% to 6.1%. More details on the measurement of proteins can be found in previous publications 11,13 …”

“…The objective of this study was to test the association between plasma levels of angiopoietin‐2, VCAM‐1 and VEGF‐A and grade 2–3 hypertension in patients treated with regorafenib. Because we aimed to validate proteins previously associated with bevacizumab‐induced hypertension in our discovery study, 11 we have tested the association of only angiopoietin‐2, VCAM‐1 and VEGF‐A, instead of all proteins measured in REGOLAND. The levels of proteins were inverse quantile normalized before performing the association tests to decrease the influence of outliers, as previously described 11 .…”

“…Because we aimed to validate proteins previously associated with bevacizumab‐induced hypertension in our discovery study, 11 we have tested the association of only angiopoietin‐2, VCAM‐1 and VEGF‐A, instead of all proteins measured in REGOLAND. The levels of proteins were inverse quantile normalized before performing the association tests to decrease the influence of outliers, as previously described 11 . The associations between protein levels and grade 2–3 hypertension were performed by calculating the odds ratio (OR) from a univariate logistic regression analysis, with hypertension as a binary outcome (grade 0–1 vs grade 2–3).…”

“…We have previously performed a discovery study using data from two randomized, double‐blind phase III clinical trials from the Cancer and Leukemia Group B (CALGB, now part of the Alliance for Clinical Trials in Oncology, Alliance), CALGB 80303 and 90401. Patients with lower plasma levels of angiopoietin‐2, VCAM‐1 and VEGF‐A were at high risk of developing severe hypertension when treated with bevacizumab 11 . Because hypertension is a side effect of the whole class of VEGF pathway inhibitors, 4 the current study aimed to validate the predictive value of angiopoietin‐2, VCAM‐1 and VEGF‐A in an additional cohort of patients treated with regorafenib.…”