Meta-analysis: Sunitinib, sorafenib increased risk for arterial thrombosis threefold

The use of the oral vascular endothelial growth factor receptor tyrosine kinase inhibitors sunitinib and sorafenib resulted in a threefold increased relative risk for arterial thrombosis, according to the results of a meta-analysis.

“These two agents have been associated with arterial thromboembolic events such as cardiac or cerebrovascular events in selected case series or clinical trials,” the researchers wrote. “Furthermore, bevacizumab (Avastin, Genentech) has recently been associated with a significant increase in the risk of arterial thromboembolic events when combined with chemotherapy.”

Researchers gathered data from relevant articles published between 1966 and 2009 and abstracts presented at the American Society of Clinical Oncology and the European Society of Medical Oncology between 2004 and 2009. Ten trials that included 10,255 patients were selected for the analysis.

In the incidence analysis, the researchers included 9,387 patients. Of these patients, 122 had an arterial thromboembolic event, an incidence of 1.4% (95% CI, 1.2%-1.6%). There was no statistically significant difference between sunitinib (Sutent, Pfizer) and sorafenib (Nexavar, Bayer) for the incidence of arterial thromboembolic events (1.3% vs. 1.7%).

When the data were stratified according to underlying malignancy — renal cell carcinoma vs. non-renal cell carcinoma — no difference in the incidence of arterial thromboembolic events was found (P=.71).

Next, the researchers examined data from three randomized studies to calculate the RR for arterial thromboembolic events in patients assigned one of these TKIs vs. control patients. Of the 989 patients assigned sunitinib or sorafenib, 22 arterial thromboembolic events occurred; six arterial thromboembolic events occurred among 868 control patients. This equaled a RR for arterial thromboembolic events of 3.03 among patients assigned sunitinib or sorafenib vs. control patients.

Choueiri TK. J Clin Oncol. 2010.doi:10.1200/JCO.2009.27.2757.