A panel of oncology experts that advises the U.S. Food and Drug Administration (FDA) voted against continuing the approval of Avastin (chemical name: bevacizumab) in combination with Taxol (chemical name: paclitaxel) to treat metastatic, HER2-negative breast cancer that hasn't been treated with chemotherapy. The expert panel, known as the Oncology Drug Advisory Committee (ODAC), voted 12 against and one for continuing the current approval. The ODAC panel also voted unanimously against approving Avastin in combination with other chemotherapy medicines to treat metastatic breast cancer.
The FDA considers the ODAC recommendations as well as research results when making a final decision about whether to continue the current approval or grant a new approval for a cancer treatment. The FDA doesn't have to follow ODAC recommendations, but usually does. These new ODAC recommendations are only about using Avastin to treat metastatic breast cancer. Avastin is approved by the FDA to treat advanced-stage lung, colon, and kidney cancer; those approvals aren't being reconsidered.
Avastin is a targeted therapy medicine that is given intravenously. 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.
ODAC experts had the following concerns about using Avastin to treat metastatic breast, HER2-negative cancer:
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), which can increase the risk of serious infection.
Based on the ODAC vote, it's likely that the FDA will no longer approve using Avastin to treat metastatic breast cancer (a final decision is expected in September 2010). Still, many doctors believe that the 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 that particular use is officially approved by the FDA. Still, the loss of approval can make it less likely that insurers will pay for Avastin to treat breast cancer.
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 talk to your doctor about:
If you are already getting Avastin and are responding to treatment, ask your doctor about the ODAC recommendations. It's likely that your doctor will recommend that you stick with your treatment plan unless it stops being effective or unacceptable side effects develop.
You can learn more about Avastin in the Breastcancer.org Targeted Therapies section.
Stay tuned to Breastcancer.org Research News for updates on the FDA decision regarding Avastin.
GAITHERSBURG, Md. (MedPage Today) -- An advisory panel has voted 12 to 1 to recommend that the FDA remove the advanced breast cancer indication from bevacizumab (Avastin), after two large clinical trials failed to demonstrate a clinically meaningful benefit of the drug, which carries serious side effects.
The Oncologic Drugs Advisory Committee voted that bevacizumab, when added to standard chemotherapy, does not extend progression-free survival long enough to be clinically meaningful in HER2-negative, metastatic breast cancer.
If the FDA follows the advice of its advisory committee -- and it usually does -- bevacizumab would still be approved to treat lung, kidney, and colon cancer. The agency will make a decision by Sept. 17.
In 2008, the FDA granted special, fast-track approval to bevacizumab manufacturer Genentech to begin marketing the drug for patients with metastatic breast cancer in combination with the chemotherapy agent paclitaxel. The "accelerated" approval was based on positive early findings from a large clinical trial sponsored by the company that found bevacizumab adds 5.5 months of progression-free survival compared with paclitaxel-only treatment.
But the two clinical trials of nearly 2,000 breast cancer patients that Genentech submitted to move from accelerated approval to standard approval failed to confirm the magnitude of progression-free survival seen in the earlier study, FDA staff reviewers and the panel concluded.
In those trials, the added time ranged from a little less than a month, to just under three months.
The panel voted unanimously -- 12 to 0 -- that the two new trials, taken together, failed to demonstrate enough benefit to using bevacizumab to warrant the drug's risks, which include a small risk of death, as well as bleeding and hypertension.
"We have definitive evidence that Avastin causes serious and life-threatening side effects," said panel chairman Wyndham Wilson, MD, PhD, chief of the lymphoma section at the National Institutes of Health. "We've seen other studies that show no overall improvement in quality of lives people have ... and there hasn't been evidence shown that it has led to clinical benefit."
In the first study, the double-blind placebo-controlled AVADO trial, researchers compared treatment with two different doses of bevacizumab paired with docetaxel with docetaxel alone in 736 patient with HER2 negative tumors who had not received chemotherapy.
In both dosing groups, bevacizumab treatment added less than a month of progression-free survival compared with the group receiving docetaxel. The advisory panel voted 13-0 that the AVADO trial failed to show that benefits of bevacizumab justify the risks.
In the second trial, RIBBON 1, Genentech tested bevacizumab with a class of chemotherapy drugs called taxanes and anthracyclines, or with capecitabine (Xeloda).
For the 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 a 1.2-month difference in median progression-free survival; adding bevacizumab to capecitabine resulted in a 2.9 month difference in median progression-free survival.
The panel didn't think that those times were clinically meaningful, even though it was longer than the progression-free survival times in the company's AVADO trial. So, on RIBBON 1, the panel voted 12-1 that the trial failed to prove that the benefits of bevacizumab outweigh the risks.
Results from a pooled analysis demonstrated no difference between treatment arms in the overall survival.
"Survival trumps everything, and we haven't shown a survival benefit here," said Ronald Richardson, MD, a medical oncologist at the Mayo Clinic.
Genentech argued that even small gains in progression-free survival are clinically meaningful and that additional weeks where tumors don't worsen translate to improved quality of life.
The committee was skeptical of that claim.
In both the RIBBON 1 and the AVADO trial, serious adverse events -- including hypertension, bleeding, and febrile neutropenia -- were higher in patients receiving bevacizumab.
Genentech stood by its claim that the drug can improve the lives of women with advanced breast cancer.
"We stand by the data we presented today on Avastin in advanced breast cancer, and believe Avastin should be an option for patients with this incurable disease," the company said in a release.
Bevacizumab is also used treat recurrent glioblastoma under accelerated approval.
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