Avastin Gets Approval for Breast Cancer, Despite Safety ConcernsFeb 26, 2008 | Parker Waichman LLP
Avastin has been approved by the Food & Drug Administration (FDA) to treat advanced breast cancer, despite a recommendation from the agency's own advisory panel that it not expand the approved uses of Avastin, and concerns over the drug's safety. In the end, the FDA decided to approve Avastin on the basis that it has been shown to slow tumor growth, even though it has not been shown to increase survival time or improve quality of life in patients with advanced breast cancer.
Avastin was approved by the FDA in 2004 to treat colon cancer, and in 2006, the agency approved it as a treatment for non-small cell lung cancer. Avastin was the first approved therapy designed to inhibit angiogenesis, the process by which new blood vessels develop and carry vital nutrients to a tumor. Avastin has been a blockbuster for Genentech, and its parent company Roche AG. For the first nine months of 2007, US sales of Avastin topped $1 billion, accounting for 27% of Genentech’s overall product sales.
Late last year, an FDA advisory panel voted 5-4 to recommend that the agency reject Genentech’s application to expand the approved uses of the drug to include advanced breast cancer. The FDA advisory panel vote came after agency staffers posted documents on the FDA website noting that while Avastin did extend the period prior to patients’ breast cancer becoming worse, treatment with the drug did not markedly increase survival time. The FDA documents also pointed out that Avastin caused serious side effects, including cardiovascular problems, bowel perforations, and a few deaths. The FDA staff said that those side effects included several patient deaths that were “probably or definitely” due to Avastin. While the FDA is not bound by the recommendations of advisory panels, it usually does follow them. For that reason, many were skeptical that Avastin would get approval as a breast cancer treatment.
But despite its safety issues, many advocates for breast cancer patients had been pushing the FDA to approve it for treating advanced breast cancer. It is estimated that about 9,500 breast cancer patients are already treated off-label with Avastin, and FDA approval will make it easier for such patients to get insurance coverage for the treatment. Some insurers are reluctant to pay for Avastin's use among breast cancer patients, which can cost $100,000 for a year's supply.
However, many in the medical community are disturbed that Avastin has been approved for breast cancer, as there are fears that it could signal a lowering of FDA standards. FDA approval for drugs targeted at cancer patients who have never been treated before is usually contingent upon data showing a drug extended, or improved the quality of, patients' lives. Avastin showed neither in a study submitted by Genentech, though the drug did slow tumor growth. Some think the FDA's Avastin decision opens the door for more cancer drugs to be approved for their tumor-shrinking capabilities, a development that has some cancer experts worried. "If FDA sets a precedent of approving a drug based on progression free survival, people are afraid they may stop looking at survival as the most important endpoint," Dr. Kay Dickersin, director of the Center for Clinical Trials at Johns Hopkins University, told the Associated Press.
The president of the National Breast Cancer Coalition also told the Associated Press that the decision marked a lowering of standards at FDA. She said the drug's effectiveness in shrinking tumors should not have outweighed safety risks, pointing to six deaths attributed to the drug in the study submitted to FDA. "All they had was progression-free survival in one trial, no increase in quality of life and patient deaths in the Avastin group," said Fran Visco. "We're very confused why FDA made this decision."