Bevacizumab Use and the Risk of Arterial and Venous Thromboembolism in Patients with High‐Grade Gliomas: A Nested Case‐Control Study

Abstract

STUDY OBJECTIVE Bevacizumab is used in the treatment of recurrent glioblastoma, but evidence is limited on the incidence of thromboembolic complications regarding the use of this drug in real-world settings. We evaluated the risk of arterial thromboembolism (ATE) and venous thromboembolism (VTE) associated with the use of bevacizumab among adults diagnosed with high-grade gliomas in a commercially insured U.S. population. DESIGN Nested case-control study. DATA SOURCE Truven Health MarketScan Commercial and Medicare Supplemental health claims databases (2009)(2010)(2011)(2012)(2013)(2014)(2015). PATIENTS A total of 2157 patients with high-grade gliomas who underwent incident (first-time) craniotomy, radiation, and concurrent temozolomide treatment between 2009 and 2015 were identified. Overall, 25 cases of ATE and 99 cases of VTE were each identified in this cohort, and each case was matched to up to 10 controls (170 for ATE and 819 for VTE) based on sex, age, quarter year of index time, and follow-up duration by using incidence density sampling without replacement from the overall cohort. Controls were at risk for the outcome of interest (ATE or VTE) at the time of case occurrence and survived at least as long as their referent case. MEASUREMENTS AND MAIN RESULTS Exposure to bevacizumab was determined during inpatient or outpatient encounters between the index date (date of the incident craniotomy) and the ATE or VTE event or corresponding matched control date. Multivariable conditional logistic regression models were used to estimate odds ratios (ORs) and 95% confidence intervals (CIs) for the risk of ATE and VTE separately. A higher proportion of patients with ATE received bevacizumab compared with controls (28% vs 17%; adjusted OR 1.51, 95% CI 0.54-4.24), but this excess in odds was not

Venous thromboembolism in children with central nervous system tumors: Comparison of an institutional cohort to a national administrative database

“…Similarly, bevacizumab use was not a significant risk factor in either cohort. Previous reports have been conflicting on the thrombogenicity of this drug 40,41 . Despite having been associated with increased VTE risk in hospitalized children previously, 28 OCP use was not a risk factor in our patient population.…”

“…Previous reports have been conflicting on the thrombogenicity of this drug. 40,41 Despite having been associated with increased VTE risk in hospitalized children previously, 28 OCP use was not a risk factor in our patient population. This may have been due to the small number of OCP-treated patients in either cohort (Tables 1 and 3).…”

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“…Although the incidence of malignant CNS tumors is higher in men [67], the incidence of VTE and bleeding was similar when considering the subgroup analysis, corroborating previous investigations [31,32,68]. Mulder et al [69] assessed the occurrence of VTE in the first six months of the follow-up and found no difference between the sexes in sub-distribution hazard ratios (SHR = 1.02; 0.98-1.07).…”

“…In studies that provided incidence values by sex (n = 9), 62.7% of participants were men (n = 1,779). Only three studies presented data on patients aged 60 years or older (28,(31)(32), totaling 163 patients with VTE out of 446 patients with CNS (36.5%).…”

Utility of Administrative Databases and Big Data on Understanding Glioma Treatment—A Systematic Review

“…28,[45][46][47][48][49][50][51][52] Another study by Lee et al showed no association between bevacizumab use and thromboembolic events. 53 One study evaluated 4,407 patients via the NSQIP database who underwent resection of a malignant brain tumor between 2007 and 2012. This study included metastatic tumors (n ¼ 1611) and malignant gliomas (n ¼ 2796).…”