Arterial Thromboembolic Events in Patients with Metastatic Carcinoma Treated with Chemotherapy and Bevacizumab

Genentech, Inc., BioOncology, 455 East Grand Ave, South San Francisco, CA 94080, USA.
Journal of the National Cancer Institute (Impact Factor: 12.58). 08/2007; 99(16):1232-9. DOI: 10.1093/jnci/djm086
Source: PubMed


Although combination treatment with bevacizumab (humanized monoclonal antibody against vascular endothelial growth factor) and chemotherapy improves survival of patients with various metastatic carcinomas, an increased risk of arterial thromboembolic events has been observed in some trials. We characterized this risk by performing post hoc analyses of randomized controlled trials that evaluated combination treatment with bevacizumab and chemotherapy versus chemotherapy alone. Low-dose aspirin was permitted in these trials, and its safety was also analyzed.
Data were pooled from five randomized controlled trials that included a total of 1745 patients with metastatic colorectal, breast, or non-small-cell lung carcinoma. The risk of an arterial or venous thromboembolic event was assessed by simple incidence rates, rates per 100 person-years, and/or hazard ratios (HRs). The association between patient characteristics and risk of an arterial thromboembolic event was investigated primarily by Cox proportional hazards regression. The relationship between low-dose aspirin and bleeding was explored by incidence rates and rates per 100 person-years.
Combined treatment with bevacizumab and chemotherapy, compared with chemotherapy alone, was associated with increased risk for an arterial thromboembolic event (HR = 2.0, 95% confidence interval [CI] = 1.05 to 3.75; P = .031) but not for a venous thromboembolic event (HR = 0.89, 95% CI = 0.66 to 1.20; P = .44). The absolute rate of developing an arterial thromboembolism was 5.5 events per 100 person-years for those receiving combination therapy and 3.1 events per 100 person-years for those receiving chemotherapy alone (ratio = 1.8, 95% CI = 0.94 to 3.33; P = .076). Development of an arterial thromboembolic event was associated with a prior arterial thromboembolic event (P<.001) or age of 65 years or older (P = .01). Baseline or on-study aspirin use was associated with modest increases in grade 3 and 4 bleeding events in both treatment groups, from 3.6% to 4.7% for bevacizumab-treated patients and from 1.7% to 2.2% for control subjects.
Combination treatment with bevacizumab and chemotherapy, compared with chemotherapy alone, was associated with an increased risk of arterial thromboembolism but not venous thromboembolism.

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Available from: James Ngai, Jan 06, 2016
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    • "The evidence for the use of aspirin prophylaxis for ATE for patients using bevacizumab is conflicting. Scappatici et al (22) reported marginally more grade 3 and 4 bleeding events among aspirin users on bevacizumab than in the control subjects (3.7 vs. 1.8%). Conversely, a pooled analysis of low-dose aspirin for primary prophylaxis for ATEs in patients undergoing chemotherapy with bevacizumab did not identify any increased bleeding risk (23). "
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    Full-text · Article · Jul 2014 · PLoS ONE
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    • "Arterial thromboembolic events were uncommon in this study, which excluded patients with a history of these events. This was in contrast to other studies in which an increase in the incidence of thromboembolic events was observed in older patients (Scappaticci et al, 2007; Cassidy et al, 2010). Our study has some limitations. "
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