Cancer Drug Avastin Raises Blood Clot Risk

Nov. 18, 2008 -- The life-extending cancer drug Avastin raises the risk of dangerous blood clots by 33%, an analysis of clinical-trial data shows.

Nearly 12% of patients taking Avastin get blood clots, with 6.3% developing clots serious enough to require treatment. However, few of these clots are fatal, find Shobha Rani Nalluri, MD; Shenhong Wu, MD, PhD; and colleagues at New York's Stony Brook University.

It's not a risk that would deter most patients with life-threatening cancers from appropriate use of Avastin. But doctors and patients should be made aware of the risk -- possibly with a black-box label, Nalluri and colleagues suggest.

A black-box warning is the highest-level warning mandated by the FDA. Avastin, manufactured by Genentech, already carries black-box warnings about increased risks of intestinal perforations, wound-healing complications, and hemorrhage.

Blood clots -- deep venous thromboembolisms (DVTs) or clots in the heart -- are one of the major causes of death in cancer patients. That's probably why a smaller 2007 study was unable to link Avastin to increased blood clot risk, Nalluri and colleagues suggest. That study reassured doctors after a 2004 FDA-Genentech warning about reports of blood clots in patients on Avastin.

The researchers analyzed data on nearly 8,000 cancer patients from 15 clinical trials of Avastin. They found that high and low doses of Avastin increase blood clot risk equally.

They also found that Avastin's blood clot risk varied according to type of cancer:

• 19.1% of colorectal cancer patients treated with Avastin had blood clots.
• 14.9% of non-small-cell lung cancer patients treated with Avastin had blood clots.
• 7.3% of breast cancer patients treated with Avastin had blood clots.
• 3% of kidney cancer patients treated with Avastin had blood clots.

Avastin is a man-made antibody that targets VEGF, a molecule essential for the growth of new blood vessels. It starves tumor cells by preventing them from forming new blood supplies. But blocking VEGF also increases clotting risk.

Thalidomide and its sister drug lenalidomide (Revlimid) also block blood vessel growth in cancer patients. Both drugs' labels already carry warnings that they increase blood clot risk. It's likely that new anti-VEGF drugs now in development will carry this risk, too.

Patients taking Avastin should be aware of the symptoms of blood clots -- and should be aware that even dangerous blood clots don't always cause symptoms.

Nalluri and colleagues report their findings in the Nov. 19 issue of The Journal of the American Medical Association.