Avastin (chemical name: bevacizumab) is approved by the U.S. Food and Drug Administration (FDA) to be used in combination with Taxol (chemical name: paclitaxel) to treat metastatic, HER2-negative breast cancer that hasn't been treated with chemotherapy. Metastatic breast cancer is cancer that has spread outside the breast to another part of the body. Avastin also is used to treat advanced-stage lung, colon, and kidney cancer. Avastin is given intravenously.
Avastin is a targeted therapy medicine. Avastin works by blocking the growth of new blood vessels that cancer cells need to grow and function. A protein called vascular endothelial growth factor (VEGF) makes new blood vessels grow in cancer cells. Avastin blocks the VEGF protein.
The FDA is considering whether to continue the approval for using Avastin with Taxol to treat metastatic breast cancer, as well as whether to approve using Avastin in combination with several other chemotherapy medicines to treat metastatic breast cancer.
When making decisions about medicine approval, the FDA asks expert panels for their opinions. For cancer medicines, the FDA consults with the Oncology Drug Advisory Committee (ODAC). The ODAC reviews FDA analysis of research results and then votes on the approval. The FDA considers the ODAC vote as well as the research results when making an approval decision.
The FDA analysis of research on Avastin shows:
In the AVADO study, 736 women diagnosed with HER2-negative, metastatic breast cancer got one of three treatments:
This was the first treatment for metastatic breast cancer the women received (called first-line treatment). Taxotere, like Taxol, is a taxane chemotherapy.
The AVADO study found that women who got both Avastin and Taxotere went a month longer before the cancer started growing again compared to women who got only Taxotere. Still, overall survival was the same for all three groups.
In the RIBBON-1 study, 1,237 women diagnosed with HER2-negative, metastatic breast cancer got one of three types of chemotherapy medicine, either in combination with Avastin or alone:
This was the first treatment for metastatic breast cancer the women received.
The RIBBON-1 study found that women who got both chemotherapy and Avastin had a longer time before the cancer grew compared to women who got only chemotherapy:
Still, overall survival was the same for all the women in RIBBON-1.
Some doctors are concerned that without better overall survival, the benefits of Avastin don't outweigh the risk of side effects and the potentially high cost of treatment. Side effects of Avastin include high blood pressure, bleeding (nosebleeds, for example), and extra protein in the urine. People treated with Avastin also may have weakness, pain, and diarrhea. Avastin also may cause other serious side effects, including a higher risk of stroke or heart problems, kidney malfunction, and reduced white blood cell count (neutropenia).
In the AVADO and RIBBON-1 studies, the women who got Avastin combined with chemotherapy were more likely to experience high blood pressure, bleeding, and low white blood cell counts with fever (suggesting possible infection) compared to women who got only chemotherapy.
Still, many doctors believe that the potential benefits of Avastin for certain women diagnosed with metastatic breast cancer are worth the risks and cost of treatment. Doctors can choose to use Avastin to treat metastatic breast cancer whether or not the particular use is officially approved by the FDA.
If you've been diagnosed with metastatic breast cancer, you and your doctor will develop a treatment plan that will likely include chemotherapy and possibly hormonal therapy and/or targeted therapy medicines such as Avastin. No matter which treatments are recommended for you, you may want to ask your doctor:
You can learn more about Avastin in the Breastcancer.org Targeted Therapies section.
Stay tuned to Breastcancer.org Research News for updates on Avastin approvals.
Please help Breastcancer.org bring you the latest news on drug approvals by making a tax-deductible donation today.
WASHINGTON (MedPage Today) -- Adding bevacizumab (Avastin) to chemotherapy drugs doesn't increase survival or improve symptoms for women with advanced breast cancer, according to FDA documents posted in advance of an advisory panel meeting on Tuesday.
Members of the Oncologic Drugs Advisory Committee will vote on whether bevacizumab should continue to be used to treat locally recurrent or metastatic HER2 negative breast cancer in women who have not previously received chemotherapy.
The analysis by FDA reviewers suggests that the panel may vote No.
The agency gave accelerated approval to bevacizumab in 2008 after early findings suggested that adding the agent to treatment with paclitaxel resulted in a 52% increase in progression-free survival with a hazard ratio of 4.88 (95% CI 0.39 to 0.61; P<0.0001) and a mean duration of progression-free survival of 5.2 months.
However there was no benefit in overall survival in the group treated with bevacizumab.
In making that approval decision, the FDA went against its Oncologic Drugs Advisory Committee 5-4 vote against fast-tracking the drug.
But accelerated approval requires the company -- in this case Genentech -- to submit more data to flesh out the early findings in order to gain the FDA's standard approval.
The advisory panel meeting on Tuesday will review whether the two new clinical trials performed by Genetech to fulfill that requirement, coupled with the earlier trial, provide enough evidence to recommend regular approval for the drug for use in advanced breast cancer.
According to the FDA staff reviewers, the new data failed to confirm the magnitude of progression-free survival seen in the earlier study.
The two new trials -- AVADO and RIBBON1 -- show that combining bevacizumab with other chemotherapy drugs did not improve overall survival, the FDA staff wrote.
In the double-blind, placebo controlled AVADO trial, 736 patients with HER2 negative tumors who had not received chemotherapy were randomized 1:1:1 to docetaxel plus placebo; 7.5mg/kg of bevacizumab and docetaxel; or 15mg/kg of bevacizumab and docetaxel.
In the lower-dose bevacizumab treatment arm, patients experienced a 30% increase in progression-free survival with a hazard ratio of 0.70 (95% CI 0.55 to 0.90). Those in the higher-dose bevacizumab group experienced a 39% increase in progression-free survival with a hazard ratio of 0.62 (95% CI 0.48 to 0.79).
In both groups, bevacizumab treatment added less than a month of progression-free survival compared with the group receiving docetaxel.
Genentech is also seeking approval to use bevacizumab with a class of chemotherapy drugs called taxanes and anthracyclines, or with capecitabine (Xeloda), and submitted the RIBBON 1 trial to support that indication.
In the double-blind RIBBON 1 study, 1,237 patients were randomized 2:1 to receive anthracycline- or taxane-based chemotherapy (n=622) or capecitabine (n=615) in combination with bevacizumab or placebo.
The addition of bevacizumab to taxane/anthracycline-based chemotherapy resulted in 36% increase in progression-free survival (HR 0.64, 95% CI 0.52 to 0.80), with an observed 1.2-month difference in median progression-free survival.
Adding bevacizumab to capecitabine resulted in a 31% increase in progression-free survival (HR 0.69, 95% CI 0.56 to 0.84), with a difference of 2.9 months in median progression-free survival.
Results from a pooled analysis demonstrated no difference between treatment arms in overall survival (HR 0.97, 95% CI 0.86 to 1.08), the FDA reviewers concluded.
"Together, these results indicate that treatment with Avastin in combination with first-line chemotherapy did not improve overall survival," the FDA reviewers wrote.
In both the RIBBON 1 and the AVADO trials, serious adverse events -- including hypertension, bleeding, and febrile neutropenia -- were higher in patients receiving bevacizumab .
In Genentech's briefing documents, the company said combined evidence from the three trials -- the early trial adding bevacizumab to paclitaxel, and the two new trials "clearly demonstrates that Avastin in combination with standard chemotherapy regimens is safe and effective for the first-line treatment of women with HER2-negative metastatic breast cancer."
The panel will vote on whether the benefits of adding bevacizumab to chemotherapy for advanced breast cancer patients outweighs the risk and whether the metastatic breast cancer indication should be removed from bevacizumab's indications.
Bevacizumab is also approved to treat lung, kidney, and colon cancer, and is used by 812,000 patients worldwide.
The FDA does not have to follow the advice of its advisory committees, but it often does.
Breastcancer.org is a non-profit organization dedicated to providing information and community to those touched by this disease. Learn more about our commitment to providing complete, accurate, and private breast cancer information.
Breastcancer.org 7 East Lancaster Avenue, 3rd Floor Ardmore, PA 19003
©2011 Breastcancer.org - All rights reserved.
