Posted: Dec 17, 2010 5:37 PM
What does this decision mean for women with advanced or spreading breast cancer?
WebMD spoke to many breast cancer experts to find out why the FDA took these steps, what will happen next, and what options will be available for women with metastatic breast cancer who are responding to this drug or who anticipated beginning treatment with Avastin. Here's what we found out:
Avastin still has FDA approval for treating advanced breast cancer. Today's FDA action starts the process of removing that approval -- but for now, it's still in place.
Avastin's maker, Genentech, has requested a formal public hearing with the FDA. There is no date set for this hearing, and the FDA can reject the request.
Even if the drug's indication for breast cancer is eventually removed, doctors will still have the option of using Avastin off-label to treat breast cancer.
"I'm sure it will be used off-label," says Francisco J. Esteva, MD, PhD, a professor in the breast medical oncology department and the director of the Breast Cancer Translational Research Laboratory at the University of Texas M.D. Anderson Cancer Center in Houston. "If a patient is being treated with Avastin and paclitaxel and is responding and doing well, I would continue its use," he says.
Lillie Shockney, RN, the administrative director of the Johns Hopkins Breast Center in Baltimore, says that women with breast cancer who were anticipating starting therapy with Avastin must reconnect with their medical oncologist to discuss the next steps.
"When the decision was made to approve Avastin for breast cancer, it was believed to be helpful and now women need to have a thoughtful discussion on how to proceed, which will likely include using another medication," she says.
"If an individual was benefiting, it would not surprise me if she decided, together with her treating oncologist, to stay on the drug because it seems to be working," she says. "If it is bringing tumor markers down and tumors are shrinking on scans, I would be saying, 'Don't take this away, because it may not work for the majority of women, but it looks like it is working for me.'"
The FDA based its decision on the results of four clinical trials that showed Avastin, when used in combination with the chemotherapy drug Taxol (paclitaxel), did not improve overall survival among women with metastatic (spreading) breast cancer.
The European Union's version of the FDA, the European Medicines Agency (EMA), also came down on Avastin's use in breast cancer, but did not go as far as the FDA. An EMA regulatory panel stated that Avastin should not be used with the chemotherapy docetaxel (Taxotere), but it can still be used with paclitaxel.
"We are pleased that the EMA has confirmed the benefits of Avastin with paclitaxel and that Avastin will continue to be available for women with metastatic breast cancer living within the European Union," says Hal Barron, MD, Genentech's chief medical officer and head of global product development, in a written statement. "We believe women living in the United States with metastatic HER2-negative breast cancer should also have Avastin as a treatment option, and, therefore, we will request a hearing with the FDA."
In 2008, the FDA approved Avastin as a breast cancer treatment for some women. That approval was fast-tracked and was based on preliminary studies that found that the drug increased progression-free survival -- the time in which women's breast cancer did not worsen.
Avastin belongs to a class of drugs called angiogenesis inhibitors, which thwarts tumors from making new new blood vessels. By preventing the growth of new blood vessels, the drug starves tumors.
But in July 2010, an FDA advisory panel voted 12-1 to remove the breast cancer indication from the drug's label because follow-up studies found no differences in overall survival. These studies also showed that progression-free survival improved by less than three months, and that there was a high rate of side effects.
The FDA's decision "will come as a disappointment to many breast cancer patients who may have benefited from the drug," Len Lichtenfeld, MD, the American Cancer Society's deputy chief medical officer, says in a written statement.
"But it is important to understand the decision was based on the advice of an independent panel of experts who noted that larger studies showed some women lives were actually shortened on the drug and that toxicities associated with the drug were significant," Lichtenfeld says. "Meanwhile, the net benefit for women taking the drug was quite modest."
Some women with metastatic breast cancer have benefited from Avastin, Lichtenfeld says, but others have been harmed.
"What we clearly need is a way for doctors to more accurately predict which women will have a better chance of benefitting from this important targeted therapy," Lichtenfeld says. "Until that tool is developed, giving all women with metastatic breast cancer Avastin may harm more women than it helps."
He points out that Avastin is still considered beneficial in treating other cancers. "Women currently on [Avastin] for the treatment of breast cancer should have a detailed discussion with their oncologists as to what course of action they should take."
The FDA's decision is "no surprise, but, of course, is disappointing," Esteva says.
"There is a subset of breast cancer patients who are likely to benefit significantly from Avastin, but we don't know who they are," he says.
Developing and validating biomarkers to predict response to Avastin among people with breast cancer could help with that. "We need to do more work to identify the population likely to benefit," Esteva says.
There are other options for people with metastatic breast cancer, he says. Other chemotherapy and biologic agents, alone or in combination, may be beneficial.
For example, paclitaxel can be used in combination with other agents, he says. These decisions must be made on a case-by-case basis with a medical oncologist.
Not everyone agrees with the FDA's decision.
Joseph Sparano, MD, a medical oncologist at Montefiore-Einstein Center for Cancer Care in the Bronx, N.Y., says that he "fundamentally disagrees with FDA assessment of the benefit risk ratio of Avastin for use in breast cancer treatment." Sparano has served as a paid speaker and consultant to Genentech on Avastin.
He says that the main issue now will be an economic one.
"This is a very useful drug and it doubles the response rate to chemotherapy and the time that disease is under control," he says. "At one year, more patients are alive, which means it is effective and safe," Sparano tells WebMD.
"This is a sad day for our patients because they will have one less effective option, and what makes it even sadder is that this drug is still available and its use will be based on who can pay for it rather than who can benefit from it," he says.
Insurers will likely not cover the off-label use of the drug. The wholesale price of Avastin (minus infusion costs) is around $7,500 a month. "This certainly will become a barrier for many patients," Sparano says.
Maurie Markman, MD, vice president of patient oncology services and the national director of medical oncology at Cancer Treatment Centers of America in Philadelphia, is also disheartened by this turn of regulatory events.
"This is a most unfortunate decision by the FDA and potentially deprives women with breast cancer use of an anti-cancer agent that has unequivocally been demonstrated to prolong time to disease progression in multiple evidence-based randomized phase 3 trials conducted by outstanding research organizations," Markman writes in an email.
"Cancer care is highly personalized and individualized [and] the decision of whether this drug should be used in management of individual patients should be determined between her and her healthcare team," he writes.
Markman has served as a member of a medical advisory board for Genentech on ovarian cancer.