Questions and Answers: Removing Metastatic Breast Cancer as an Indication from Avastin’s Product Labeling
What is happening to the indication for metastatic breast cancer?
FDA Commissioner Margaret Hamburg is revoking the agency’s accelerated approval of the breast cancer indication for Avastin (bevacizumab), manufactured by Genentech. Avastin used for metastatic breast cancer has not been shown to provide a benefit, in terms of delay in the growth of tumors, that would justify its serious and potentially life-threatening risks. Nor is there evidence that use of Avastin will either help women with breast cancer live longer or improve their quality of life.
Why was this decision made? What is FDA’s authority to remove the breast cancer indication from the drug’s labeling?
By law, drugs must be demonstrated to be safe and effective for their intended use in order to merit FDA approval. Avastin for metastatic breast cancer was approved under the FDA’s accelerated approval program that provides earlier patient access to promising new drugs for treatment of patients with serious and life-threatening diseases. Such drugs may receive accelerated approval while confirmatory clinical trials are being conducted to verify that the drugs are truly effective.
Regulations state that if the confirmatory studies fail to verify clinical benefit, or if other evidence demonstrates that the product is not safe or effective under its conditions for use, FDA may withdraw approval. Genentech did conduct studies but these studies were not confirmatory; they did not demonstrate that Avastin provides benefits in treating metastatic breast cancer that outweigh its risks. Based on those findings, FDA’s Center for Drug Evaluation and Research (CDER) proposed removing the breast cancer indication from Avastin’s label. Genentech opposed that decision and requested that the FDA Commissioner convene a hearing, which took place on June 28-29. Both Genentech and CDER were parties to that hearing. By law, the outcome of that hearing must be decided by the FDA Commissioner.
Today’s decision was based on a review of the arguments and evidence presented at the hearing, briefs filed by both CDER and Genentech before and after the hearing, public comments and data from multiple clinical trials. Other than in its role as a party to the hearing, CDER was not involved in making the final decision.
Did an independent advisory committee consider the question of whether FDA should withdraw approval of the breast cancer indication?
Yes. The FDA's Oncologic Drugs Advisory Committee participated in the June 2011 hearing and voted 6-0 in favor of withdrawal of approval of the breast cancer indication.
What are the potential risks of taking Avastin?
Women who take Avastin for metastatic breast cancer risk potentially life-threatening or serious side effects, such as bleeding and hemorrhaging; heart attack or heart failure; severe blood pressure; and the development of perforations in different parts of the body such as the nose, stomach and intestines.
These are the considerable risks of taking Avastin and can be justified only if there is good evidence that the use of the drug will benefit the patient. For some kinds of cancers, Avastin has been shown, by rigorous scientific testing, to provide a benefit that justifies its risks. After reviewing the available studies, however, it is clear that there is no proof of a benefit in breast cancer patients that would justify those risks. Avastin has not been shown to provide a benefit, in terms of delay in tumor growth, that would justify its risks. Nor is there evidence that use of Avastin will either help women with breast cancer live longer or improve their quality of life.
Does this mean that Avastin will no longer be available?
No, this action will not result in any changes to the other approved indications. Avastin will continue to be an approved treatment option for patients with certain kinds of advanced colon, lung, kidney, and brain (glioblastoma) cancers. Avastin will thus remain on the market labeled for those indications.
What does it mean to remove an indication from a product label?
When FDA approves a medication, the approval is limited to specific indications for use. These indications for use are discussed in a package insert that explains to physicians how the drug is to be used and what the supporting data show. As a result of today’s decision, any language discussing a metastatic breast cancer indication must be removed from the package insert of the product.
When does this labeling change become effective?
The approval for metastatic breast cancer is being withdrawn immediately. Genentech will now have to revise its labeling to make sure that all mention of the breast cancer indication is removed and will submit its revised labeling to FDA for approval. While these changes are being made, existing product with labeling that makes mention of the breast cancer indication may remain on the market. Even after the labeling change to remove the breast cancer indication, Avastin will remain on the market labeled for its approved indications.
What should patients do who are currently being treated with Avastin for their breast cancer?
Patients currently receiving Avastin for breast cancer should speak with their oncologists (cancer physicians) about whether to continue their treatment or explore other treatment options. Oncologists should use their medical judgment when deciding whether their patients should continue using Avastin with the drug paclitaxel, take paclitaxel alone, or consider other treatment options.
Did FDA factor the cost of Avastin into its decision?
No. FDA does not factor costs into its drug approvals or safety related decisions.
If the drug is shown to work in a certain type of breast cancer or in certain patients with breast cancer, would FDA consider including this information in the product labeling?
If the company conducts further clinical studies that show Avastin's benefits outweigh its risks for a specific group of patients and submits the data to FDA for approval, then FDA would consider adding this information to the product labeling.
What other treatment alternatives exist for women with metastatic breast cancer?
There are other drugs that have been approved for use, either alone or in combination, to treat metastatic breast cancer.
Table 1 – Other Agents Approved by the FDA for use in Metastatic Breast Cancer
Year of Approval
Metastatic breast cancer
2nd and 3rd line MBC*
Capecitabine + Docetaxel Abraxane
1st line MBC*
Trastuzumab +Paclitaxel Gemcitabine + Paclitaxel
* First-line means treatment of individuals with MBC who have not received previous chemotherapy for MBC. Second-line is treatment of individuals with MBC who have previously received chemotherapy for MBC. Third-line is treatment of those who have received chemotherapy on two or more occasions for MBC.