Avastin may increase risk of neural bleeding and stroke in patients

http://www.ft.com/cms/s/2/f4bf6a1a-857b-11dd-a1ac-0000779fd18c.html

Avastin (bevacizumab) may increase the risk of neural bleeding and stroke in a small population of patients with glioblastoma multiforme, according to several physicians interviewed by Pharmawire. The gravity of this side-effect should be carefully studied, they added.

The drug acts by targeting vascular endothelial growth factor (VEGF) and is thought to act by blocking the formation of new blood vessels (angiogenesis). The drug is approved by the FDA for the treatment of patients with non-small cell lung cancer, colorectal cancer and metastatic breast cancer. Avastin is currently undergoing Phase II clinical studies in patients with glioblastoma multiforme.

A significant side-effect of Avastin is that the drug’s administration may cause bleeding complications in the brain, according to Dr Steven Wong, a brain cancer expert at Harvard University. Genentech did not want to initiate clinical studies of Avastin in glioblastoma because the neural bleeding risk was so heavily feared, Wong said.

Serious bleeding complications occur in a little less than 5% of the patients who receive Avastin, Wong explained. Also, administering the drug in the time frame of four to six weeks before and after surgery could increase the risk of bleeding in the brain, he added.

A Genentech spokesperson said safety concerns did not emerge in the Phase II study of Avastin in patients with glioblastoma.

However, due to lack of data from randomized controlled clinical studies, physicians estimated that anywhere from 2% to approximately 70% of patients given the drug may experience the side-effect of bleeding. Treatment with Avastin has also caused stroke and hemorrhage in patients with colon and non-small cell lung cancers who have brain metastases, according to oncologists that treat patients with those diseases.

Dr William Leenders, who is currently studying Avastin in this indication, and a physician in the department of pathology at the Raboud University Nijmen Medical Centre, said the likelihood of experiencing a neural hemorrhage after receiving Avastin is approximately 70%. Physicians cannot do anything to minimize patients’ potential risk of bleeding after receiving Avastin and many physicians are wary of administering the drug for glioblastoma due to this risk, Leenders said. Genentech has not seen such a high number of reported adverse events associated with Avastin in a clinical trial for any tumor type, a Genentech spokesperson noted. If this number is based on anecdotal reports from physicians, then it could be very misleading, the spokesperson said. In a Phase II trial for relapsed glioblastoma multiforme, Avastin was well tolerated and associated with low rates of bleeding, she added. Still, Dr Maria Juarez, a specialist at the Cancer Institute of Dallas noted that the rate of neural bleeding in past clinical studies of Avastin was so low, because they excluded patients with brain metastases. Avastin can increase the risk of hemorrhagic stroke, systemic stroke and blood pressure, Juarez said.