Cancer drug may be associated with increased risk of blood clots

An analysis of randomized, controlled trials indicates that use of bevacizumab (Avastin) is associated with an increased risk of venous thromboembolism, researchers reported in JAMA (2008; 300:2277-85).

Bevacizumab is a recombinant humanized monoclonal antibody to vascular endothelial growth factor that is used in the treatment of cancer. It is currently being investigated in phase III trials for the treatment of advanced renal cell carcinoma.

First author Shobha Rani Nalluri, MD, of Stony Brook University, Stony Brook, NY, and colleagues conducted a meta-analysis of 15 randomized, controlled trials, which included a total of 7,956 patients with a variety of advanced solid tumors. Among patients receiving bevacizumab, the incidences of all-grade venous thromboembolism and high-grade venous thromboembolism were 11.9% and 6.3%, respectively, reported Dr. Nalluri, who worked on the study with Shenhong Wu, MD, PhD, and colleagues.

The risk of developing venous thromboembolism was 33% greater with bevacizumab than with controls. The risk was significantly increased for both all-grade and high-grade venous thromboembolism. Both a high dose (5 mg/kg per week) and low dose (2.5 mg/kg per week) of bevacizumab were associated with a 31% increased risk of venous thromboembolism.

“The association of venous thromboembolism with new agents presents a challenge for recognition because many randomized, controlled trials may not be powered to reveal a significant relationship,” Dr. Nalluri and colleagues wrote. “Our meta-analysis of 15 randomized, controlled trials has overcome this limitation of individual trials and demonstrated that bevacizumab may be associated with a significantly increased risk of venous thromboembolism in patients with a variety of metastatic solid tumors.

“The increased risk is observed not only for all-grade venous thromboembolism, but also for clinically significant high-grade venous thromboembolism. This finding will help physicians and patients to recognize the risk of venous thromboembolism with the administration of bevacizumab.”