Researchers involved in five randomized trials have reported that treatment of metastatic colorectal cancer, breast cancer, or non–small lung cancer with a combination of Avastin (bevacizumab) and chemotherapy results in a higher risk of arterial thromboembolic events than treatment with chemotherapy alone. These results were published in the August 15, 2007 issue of the Journal of the National Cancer Institute.

Avastin is a drug that blocks a protein known as vascular endothelial growth factor (VEGF). VEGF stimulates the growth of new blood vessels. Drugs that interfere with VEGF can slow or stop the growth of cancer cells. In addition, drugs that interfere with VEGF may improve the delivery of chemotherapy to cancer cells by normalizing blood supply. While clinical trials have indicated that the combination of Avastin and chemotherapy improves survival among patients with certain types of metastatic cancer, some of these trials have also suggested that this treatment combination may increase the risk of arterial thromboembolic events. In August of 2004, the US Food and Drug Administration (FDA) and Genentech, Inc. issued an important drug warning to healthcare providers that there was evidence of an increased risk of serious arterial thromboembolic events, including cerebrovascular accident, myocardial infarctions, transient ischemic attacks, and angina related to Avastin. The risk of fatal arterial thrombotic events was also increased.

To provide additional information about the risk of thromboembolism in patients treated with Avastin and chemotherapy, researchers combined information from five clinical trials. These trials enrolled a total of 1,745 patients with metastatic colorectal, breast, or non–small cell lung cancer. Each of the trials compared the combination of Avastin and chemotherapy to chemotherapy alone.

Patients were evaluated for arterial thromboembolic events, including angina pectoris, arterial thrombosis, cerebral infarct, cerebral ischemia, cerebrovascular accident, myocardial infarction, or myocardial ischemia.

• Risk of an arterial thromboembolic event was 3.1 per 100 person-years among patients treated with chemotherapy alone and 5.5 per 100 person-years among patients treated with Avastin and chemotherapy.
• Other factors that increased the risk of arterial thromboembolism were older age (age 65 or older) and history of arterial blood clots.
• Risk of venous clots was not increased among patients treated with Avastin and chemotherapy.
• They also observed that aspirin increased bleeding in Avastin and non-Avastin treated patients with a slightly higher incidence in the Avastin group.

The researchers concluded that compared to chemotherapy alone, the combination of chemotherapy and Avastin increases the risk of blood clots in the arteries.

Comments: These data are similar to those published in 2004 which led to concern by the FDA and led to changes in labeling. These data should be helpful for counseling patients about the risks and benefits of Avastin therapy.

Reference: Scappaticci FA, Skillings JR, Holden SN, et al. Arterial thromboembolic events in patients with metastatic carcinoma treated with chemotherapy and bevacizumab. Journal of the National Cancer Institute. 2007; 99:1232-9.

Related News:

Addition of Avastin® to Gemzar®/Platinol® Combination Improves Progression-free Survival in NSCLC (6/22/2007)

Avastin® Improves PFS Following XELOX or FOLFOX for Colorectal Cancer (10/13/2006)

FDA Requests Safety and Efficacy Updates for Avastin® (9/15/2006)

Updated Results from Phase III Trial Evaluating Addition of Avastin® in Advanced Breast Cancer (12/13/2005)

FDA, Genentech warn of increased cardiovascular risks associated with Avastin (8/13/2004)