Putting Patients First: The Need for Better Standards at the FDA

by Barbara A. Brenner

I have written frequently about the Food and Drug Administration for this column. It has never seemed more important than now to spell out in the clearest possible terms what breast cancer patients need from the FDA and why.

The FDA’s recent approval of Avastin (bevacizumab) is the latest case in point. In an open letter to the FDA, we pointed out that, with this decision, the agency has lowered the bar on the approval of cancer drugs.

Every day seems to bring a new story either about the dangers of drugs long ago approved by the agency or about the undue influence of the pharmaceutical/biotech industry on FDA decisions. As the only national breast cancer organization that has declared its complete independence from funding by pharmaceutical companies (see BCA’s Corporate Contributions Policy), BCA is in a unique position to articulate a clear standard for approval of new breast cancer drugs.

In addition, as a result of our in-depth strategic planning process, we at BCA have decided to increase our FDA advocacy efforts, so it is critically important that we be clear for ourselves and for our constituents about how we see the drug approval situation and how we would like to transform it.

There are many drugs approved for breast cancer. (For a list of breast cancer treatment drugs available free or at discounted rates, see our guide to patient assistance programs.) Given this environment, we at BCA believe that any new drug approved for the treatment of breast cancer must be demonstrated to be able do at least one of the following three things:

  • Extend the life of the patient, i.e., improve overall survival (OS).
  • Improve the patient’s quality of life.
  • Cost less than therapies already available.

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Improve Overall Survival

Robert Erwin’s article in this issue puts in context how the FDA’s recent approval of Avastin for breast cancer treatment came about and why the ruling was so controversial. The debate over Avastin centers on whether the drug’s ability to improve progression-free survival (PFS) for some patients should justify its approval for the treatment of metastatic breast cancer patients. While PFS is used increasingly in the cancer field as a surrogate for overall survival (OS), this substitute standard is only useful if, in fact, the surrogate standard can be shown to correlate with what it was meant to stand for: overall survival. In the case of Avastin, as presented to the FDA in December, PFS improved but OS did not. So, consistent with the standard enumerated above, BCA opposed approval of Avastin for breast cancer at the time and was gravely disappointed that the FDA commissioner ignored the recommendation of his committee and granted Genentech’s application.

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Improve Quality of Life

BCA’s view is that even if a drug does not improve the chances of survival, it should be approved for breast cancer if it can be demonstrated to improve the quality of life for breast cancer patients. This argument, too, surfaced in the recent Avastin debate. While some patients say that they felt better on Avastin than they have on systemic chemotherapy drugs, these anecdotal reports do not amount to a systematic evaluation of the quality of life for patients on the drug. In trials where patients know that they are receiving the drug that is being evaluated, it is impossible to objectively gauge the impact of the drug on quality of life. Instead, quality of life assessments must be made in blinded trials (where the patients don’t know what drug they are receiving) and must use established quality of life criteria to evaluate the results.

Since the Avastin trial that Genentech presented to the FDA was an “open label” trial, where patients knew what drug they were receiving, there was no unbiased information about quality of life available for the FDA to consider. Again, for this reason, BCA opposed approval of Avastin for breast cancer.

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Less Expensive Therapies

The FDA’s mission statement reads in part that the agency is “responsible for advancing the public health by helping to speed innovations that make medicines and foods more effective, safer, andmore affordable” (emphasis added). Despite this statement, the FDA is currently prohibited by law from considering cost when it decides whether to approve new drugs for marketing or existing drugs for expanded use.

Nonetheless, with the emergence of biotech therapies being marketed at breathtaking prices, we ignore at our peril the impact of the cost of new cancer drugs on the health care system and those who are forced to rely on it. So, while BCA cannot and will not argue to the FDA that it should deny approval for a drug because of cost (Avastin will reportedly cost just under $100,000 a year for breast cancer patients), we will engage with other cancer organizations, policy makers, and the drug manufacturers themselves to try to assure that any new cancer drug that doesn’t either extend life or improve the quality of life at least costs less than other treatments currently available.

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Safety and Effectiveness—How Can We Tell?

Of course, none of the standards that BCA argues for in its FDA advocacy matters if the drug under consideration has not been shown to be both safe and effective. As drugs move quickly through the approval pipeline at the FDA, the challenge of assuring drug safety becomes more daunting. After all, it may take years for all the side effects of new treatments to be understood.

In the current drug approval environment, it becomes essential that the FDA follow two additional requirements in approving new treatments:

  1. No new treatment or expanded marketing should be approved unless at least two well-designed clinical trials have shown the benefits claimed for the drug. While this used to be required by FDA staff, more recent approvals have too often been based on a single trial. (For example, the FDA’s recent approval of the use of Herceptin as monotherapy in the adjuvant setting for breast cancer was based on one-year follow-up from a single trial (www.medpagetoday.com/HematologyOncology/BreastCancer/tb/8044).
  2. Any new approval of a drug should be accompanied by a requirement that the drug company conduct extensive and careful post-marketing studies, and report the results to the FDA and the general public. Only with post-marketing studies will we be able to understand what a drug’s long-term effects are.

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We are well aware at BCA that there are many individuals and many other cancer organizations that take a different view from ours. But the stand we take is the one we believe to be in the best interests of breast cancer patients and the people who care about them. As these matters continue to be debated at the FDA and beyond, BCA will articulate its concerns about the drug approval process and work to improve it. We will also work with our many allies to make sure that the FDA has the necessary resources to protect the public’s health. X

We are well aware at BCA that there are many individuals and many other cancer organizations that take a different view from ours. But the stand we take is the one we believe to be in the best interests of breast cancer patients and the people who care about them. As these matters continue to be debated at the FDA and beyond, BCA will articulate its concerns about the drug approval process and work to improve it. We will also work with our many allies to make sure that the FDA has the necessary resources to protect the public’s health.

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