Avastin (bevacizumab) is a new type of drug approved to treat a wide variety of cancers, including colon, lung, kidney and brain cancer. “Off label” use of Avastin for eye disease has caused blindness. Recently, the FDA revoked Avastin’s approval for breast cancer, because it does not increase a person’s overall survival endpoint, and carries high risk of serious, life-threatening side effects (blood clots, ovarian failure, blindness, and jaw deterioration). Despite these risks, Avastin has not been recalled, and it may still be prescribed as an “off label” treatment.
UPDATE: FDA Warning for Avastin Eye Infections
March 20, 2013 — The FDA and a compounding pharmacy have issued a recall after contaminated lots of Avastin were linked to 5 cases of eye infections. Click here to read more.
What is Avastin?
Avastin is the brand name for the drug bevacizumab, created by Genentech, Inc. It was approved by the FDA in 2005 for first-line treatment of patients with malignant colorectal cancer. Since 2005, Avastin has gained approval for a wide variety of cancer: lung cancer (2006), breast cancer (2008), brain cancer (2009), and kidney cancer (2009).
Avastin is the first FDA-approved drug in new type of cancer medications. It works by preventing the formation of new blood vessels, in a process known as angiogenesis, and thereby inhibits the growth of cancerous tissue. Avastin has been shown to extend malignant colorectal cancer patients’ lives by about five months when given in combination with standard chemotherapy drugs.
Because Avastin showed promise in early trials, it was accelerated through the FDA approval process. When a drug is fast-tracked through the approval process, the FDA grants a drug temporary approval while conducting more thorough clinical trials. The FDA can revoke approval as more studies are completed. This approval method allows patients with life-threatening diseases to have access to the cutting edge of treatment.
Avastin is one of the most popular cancer drugs in history. Its effectiveness against colorectal cancer is particularly exciting, because colorectal cancer is the third most common cancer affecting men and women in the U.S., the second leading cause of cancer-related death, and one of the most commonly diagnosed cancers in the U.S. — approximately 147,500 new cases were diagnosed in 2003.
Avastin Causing Blindness in “Off-Label” Use
August 2011 — The FDA issued another Avastin safety warning after 12 people with eye diseases were blinded by doctors who injected their patients with small doses of Avastin. The FDA has not approved Avastin for the treatment of eye diseases.
Though it is an off-label use, doctors commonly use Avastin for the treatment of age-related macular degeneration and other eye diseases. The reasoning is financially-motivated: one dose of Avastin costs roughly $50/injection. This is significantly cheaper than Lucentis, a similar drug created by Genentech, Inc. Lucentis has been approved for the treatment of eye diseases but costs $2000/injection. Physicians believe that the reason Avastin is causing blindness is not because the drug is ineffective, but rather because the vials of Avastin must be repackaged into smaller doses for injection into the eye. The extra handling increases the risk of bacterial contamination.
Avastin Breast Cancer Approval Revoked
This announcement has been anticipated since Avastin failed Phase III clinical trials last year, showing a lack of survival benefit and high risk of severe side effects. Though it showed an 18% improvement in response rate of the cancer, there was no difference in the primary overall survival endpoint at 25 months.
Serious side effects that outweigh the benefit of Avastin include severe high blood pressure, bleeding and hemorrhaging, heart attack or heart failure, the development of perforations in different parts of the body such as the nose, stomach, and intestines.
FDA Safety Warnings
On September 30, 2011, the FDA updated the safety label of Avastin because of the following serious risks associated with taking the medication:
- Ovarian Failure New cases of ovarian failure were identified in 34 percent (32/95) of women receiving Avastin compared with 2 percent (2/84) of women receiving chemotherapy alone.
- Venous Thrombolic Events (VTE) In a randomized study of 1,401 patients with metastatic colorectal cancer, the overall incidence of bleeding was 27.4 percent in the patients treated with bevacizumab compared with 20.9 percent in the patients treated with chemotherapy alone.
- Osteonecrosis of the jaw (ONJ) is a severe bone disease that occurs when a facial bone begins to starve from a permanent or temporary lack of blood. This side effect is probably related to the anti-angiogenic properties of Avastin.
Other safety warnings:
- September 27, 2006 – The FDA and Genentech, Inc. issued a safety warning after finding evidence of an increased risk of reversible posterior leukoencephalopathy syndrome (RPLS), a rare brain-capillary leak syndrome associated with hypertension, fluid retention, and cytoxic effects of immunosuppressive drugs on the vascular endothelium.
- August 12, 2004 — The FDA and Genentech issued a safety warning after finding an increased risk of serious arterial thrombolic events, including cerebrovascular accident, myocardial infarctions, transient ischemic attacks, angina, and fatal arterial thrombotic events. The risks of a serious arterial thrombotic event was approximately two-fold higher in patients taking Avastin, with an estimated overall rate of up to 5 percent.