Meta-analysis data show 33% higher risk for VTE with bevacizumab

Highest incidence was observed in patients with colorectal cancer.

The use of bevacizumab in patients with various advanced solid tumors was associated with an increased risk for all- and high-grade venous thromboembolism, according to data from a meta-analysis published in JAMA.

To determine the overall risk for venous thromboembolism associated with bevacizumab, researchers from Stony Brook University and Kidney Doctor PLLC, both in New York, used PubMed and Web of Science to search for randomized controlled trials published from January 1966 to January 2008.

Data for 7,956 patients from 15 randomized trials that used standard antineoplastic therapy with (n=4,292) and without bevacizumab (n=3,664) were included in the analysis.

The researchers identified 2,279 patients with colorectal cancer, non–small cell lung cancer, breast cancer and renal cell cancer from six studies with venous thromboembolism data. The incidence of all-grade venous thromboembolism among patients assigned to bevacizumab ranged from 3% to 19.1%. The highest incidence occurred in two trials of patients with advanced colorectal cancer and the lowest occurred in a trial of patients with metastatic renal cell carcinoma. In these patients, the summary incidence of all-grade venous thromboembolism was 11.9% (95% CI, 6.8%-19.9%).

The incidence of high-grade venous thromboembolism was also higher among patients assigned to bevacizumab. The researchers identified 3,795 patients with a variety of advanced solid tumors from 13 studies with venous thromboembolism data. The incidence of high-grade venous thromboembolism was between 2% and 17%. The highest incidence occurred in patients with malignant mesothelioma and the lowest occurred in those with metastatic renal cell carcinoma. High-grade venous thromboembolism had a summary incidence of 6.3% (95% CI, 4.8%-8.3%) among these patients.

"The findings of this meta-analysis in JAMA, a review of previously published studies, are consistent with what is already in the Avastin label," a Genentech representative told HemOnc Today. "Avastin's safety is well characterized in its FDA approved indications, and more than 350,000 people with advanced cancer worldwide have received the drug since its FDA approval in 2004."

Risk for venous thromboembolism

The researchers calculated the RR for venous thromboembolism related to bevacizumab compared with controls. RRs for all-grade venous thromboembolism among patients with advanced malignancies were between 2% and 18%. RRs for high-grade venous thromboembolism were between 0.7% and 9.5%.

Overall, the RR for venous thromboembolism for bevacizumab vs. control was 1.33 (95% CI, 1.13-1.56). According to the researchers, the risk for venous thromboembolism after treatment with bevacizumab was 33% higher than for controls.

The researchers reported a summary RR of 1.29 (95% CI, 1.03-1.63) for all-grade venous thromboembolism and 1.38 (95% CI, 1.12-1.70) for high-grade venous thromboembolism.

Bevacizumab dose affected venous thromboembolism risk; among 11 trials with 4,858 patients, RR for 5 mg/kg per week was 1.31 (95% CI, 1.02-1.68). Among seven trials of 3,594 patients, RR for 2.5 mg/kg per week was also 1.31 (95% CI, 1.08-1.60)

The summary incidence of high-grade venous thromboembolism differed among tumors — 7.3% for colorectal cancer, 6.5% for NSCLC and 3.9% for breast cancer. Patients with renal cancer had the lowest incidence of high-grade venous thromboembolism at 2%.

“Future studies are needed to investigate the prevention and management of venous thromboembolism associated with bevacizumab,” the researchers wrote. – by Stacey L. Adams