Arterial thromboembolic events in patients with metastatic carcinoma treated with chemotherapy and bevacizumab.

By F. Scappaticci, J. Skillings, S. Holden, H. Gerber, K. Miller, F. Kabbinavar, E. Bergsland, J. Ngai, E. Holmgren, Jiuzhou Wang and 1 more. Journal of the National Cancer Institute, 2007

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BACKGROUND 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. METHODS 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. RESULTS 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. CONCLUSIONS Combination treatment with bevacizumab and chemotherapy, compared with chemotherapy alone, was associated with an increased risk of arterial thromboembolism but not venous thromboembolism.

Subfields: Cardiology and Cardiovascular Medicine, Molecular Biology, Oncology

View Paper: https://www.semanticscholar.org/paper/2d05d83ac1352a9a859145ae1ac287be4baa1843

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Citations in the corpus

2016 ESC Position Paper on cancer treatments and cardiovascular toxicity developed under the auspices of the ESC Committee for Practice Guidelines: The Task Force for cancer treatments and cardiovascular toxicity of the European Society of Cardiology (ESC). (2016, background): “8% in metastatic diseases.(60,122) A recent meta-analysis on the risk of arterial thrombosis induced by anti-VEGF small molecule TKIs found an overall”
Ten years of anti-vascular endothelial growth factor therapy (2016, background): “…, although subsequent studies revealed infrequent adverse events including gastrointestinal perforations, nephrotic syndrome and arterial thromboembolic complications such as myocardial infarction and stroke, especially in patients with a prior thromboembolic event or of age 65 or older 69,71,72 .”
Cardiovascular complications of cancer therapy: incidence, pathogenesis, diagnosis, and management. (2009, background): “ompared with the control group, respectively (93).”
2016 ESC Position Paper on cancer treatments and cardiovascular toxicity developed under the auspices of the ESC Committee for Practice Guidelines (2016, background): “8% in metastatic diseases.(60,122) A recent meta-analysis on the risk of arterial thrombosis induced by anti-VEGF small molecule TKIs found an overall”
The safety and side effects of monoclonal antibodies (2010, background): “pdf">Bevacizumab (Avastin; Genentech) is a humanized mAb against vascular endothelial growth factor (VEGF) that has been associated with arterial (but not venous) thromboembolic event”