Last week, the FDA made a surprising decision by approving Genentech’s Avastin to treat metastatic breast cancer. And the decision is seen as a possible shift in standards for assessing the effectiveness of cancer meds, because the agency granted approval based on progression-free survival - which is another way of saying the drug slowed tumor growth - rather than whether the drug extended life.

Not everyone, however, was pleased by the FDA, which actually ignored the advice of its own advisory panel in granting approval. In fact, a Pharmalot readers poll found that 58 percent of 166 respondents thought the FDA erred. For Barbara Brenner, a breast-cancer survivor and executive director of Breast Cancer Action, a patient advocacy group, the displeasure goes beyond the risk of serious side effects associated with Avastin. In a recent conversation, she spoke about her concerns and objections. Here is an excerpt…

Pharmalot: What is the central issue, as you see it, raised by the FDA action?
Brenner: In my view, it’s whether the FDA was going to change its standard for approval. Historically, approval was based on two things - patients had to live longer, which is overall surival. Or patients would have an improved quality of life. But a lot of drugs can make a patient very sick and so there’s a trade-off between how long one will live (on a given medication) and the quality of life that occurs.

Pharmalot: What happened this time?
Brenner: They chose progression-free survival. And in this case, there was no evidence that the drug improved the quality of life or extended life, but did show that it slowed the growth of a tumor. But that’s something you measure with a CT scan; it’s not something the patient will feel. That’s not to say we’re opposed to progression-free survival as a standard. We’re not opposed. But the product should also improve the quality of life.

Pharmalot: But how do we know that slowing tumor growth won’t yield a benefit that, down the road, doesn’t improve quality of life?
Brenner: The test for a drug should not be whether it might work. You don’t want to say ‘Let’s put in it on the market and see if that happens.’ There has to be safety and effectiveness, and that means effective for something that can be measured. In this case, Avastin has some very serious side effects (including high blood pressure and death). It’s not cotton candy.

Pharmalot: But have approval standards really changed?
Brenner: I think so. I think this changed standards for all cancer medications, anyway. You know, Richard Pazdur (who heads the FDA Office of Oncologic Drugs) said the reason was that Avastin provided a direct clinical benefit. But that’s progression-free survival. I have no idea, in fact, what that means. Maybe that’s supposed to be a substitute for quality of life. But measuring something in the clinic may not have meaning for patients.

Pharmalot: Why do you think the FDA ignored its own panel?
Brenner: The big change here is the rigorousness required for clinical trials. For Avastin, Genentech submitted a study known as E2100, but it was from the NCI (National Cancer Institute) and while it was randomized, it was also open label. For registration trials, the FDA has, historically, required a higher standard than what the NCI requires. They’ve changed the game, in other words. And they’ve now told every drug company that it’s open game. Work with NCI, find a study, come to us and we’re likely to approve the drug.

Pharmalot: There was a placebo-controlled study, though.
Brenner: Yes, it was called Avado, but the results weren’t actually released until earlier this month. They never mentioned it at the ODAC meeting in December (the FDA Oncologic Drugs Advisory Committee meeting). I believe their strategy was this - if we can get a drug approved without a registration trial, then the registration trial is just icing on the cake. They’re saying ‘On one hand, we have enough information now based on a trial not up to FDA standards, but just in case, we’ll release a trial that is up to FDA standards.’ There were also editorials in The Wall Street Journal about this. Look at the timing - it was just before the FDA was due to make a decision. I think they used the Avado trial to put pressure on the agency.

Pharmalot: Nonetheless, why shouldn’t a woman talk to her doctor about this as an option?
Brenner: This is really about marketing. Look, maybe doctors need this drug as an option. But it’s available off-label, anyway. Should patients talk to their doctors about Avastin, and know the risks and benefits, sure? But the big elephant in the room is the money this will cost. This drug will cost about $100,000. And remember, it was approved for use in combination with Taxol, so there’s another cost. Genentech says it has a patient assistance program, and the drug will be available for anyone with household income below $100,000. But it’s capped at $55,000 and the median income in the US is less than that. The numbers don’t add up - except for Genentech, which is going to realize $1 billion or more in additional revenue.