Time to get back up on my soap box.
Next month the FDA is supposed to consider taking the unique, first-time-ever step of revoking a drug’s indication not because it’s dangerous, but because it doesn’t work well enough to offset its risks. Never mind that it costs about $8,000 a month.
The drug is Avastin (bevacizumab), a targeted monoclonal antibody that prevents tumors from creating and maintaining their own blood supply, a process called angiogenesis. Without oxygen and nutrients from blood, tumors can’t keep growing.
Avastin is the world’s best-selling cancer drug, approved for use with chemotherapy to treat lung cancer and metastatic colorectal and breast cancer. It is also being investigated (and, likely, being prescribed off label) for numerous other cancers. The problem comes with breast cancer.
Avastin was approved for breast cancer under an FDA program called “accelerated approval” in which the agency provides “conditional” approval for a lifesaving drug that appears effective so as to get it to patients quickly while requiring that the manufacturer conduct more studies demonstrating its long-term effectiveness. About 90 drugs have been approved under the accelerated approval program in the past 20 years and none has ever had its approval revoked (one was pulled from the market by the manufacturer after post-marketing studies showed it was not effective and it actually increased the risk of death in patients using it).
In the case of Avastin, a single, late-stage clinical trial demonstrated that Avastin plus chemotherapy increased progression-free survival (or the amount of time until the cancer began growing again) by 5 months compared to standard therapy. What the trial didn’t show, however, was if the drug increased life expectancy, the gold standard of cancer trials. In other words, did women taking Avastin live longer than women with similar disease who didn’t take it?
Apparently not. Results from two other trials conducted by the drug’s manufacturer, Roche/Genentech found that the drug only extended progression-free survival between one and three months, with no improvement in overall survival. The company, however, cites evidence that the drug reduced the risk of progression or death (a combined endpoint) by 31 percent to 52 percent.
Given the potential risks of Avastin, including holes in your stomach or intestines, bleeding, blood clots, and high blood pressure, these trials tipped the balance away from benefits towards risks. Thus, early last month an FDA committee recommended that the breast cancer indication for Avastin be revoked. The full FDA is set to rule on the issue next month.
There’s a lot of rhetoric in the media and blogosphere that the FDA wants to revoke the indication for Avastin because of the cost. While the price tag for Avastin — like most other targeted cancer therapies — is enormous, and should be considered in any decision on its fate, the FDA, unlike the British and European “FDAs” is not allowed to consider cost when making decisions — only clinical data. That may change — and should change, in my opinion — under healthcare reform.
But I digress.
If the FDA sides with the committee recommendation, Avastin will still be on the market and doctors could still prescribe it off label to women with breast cancer. But without an official indication, insurance companies and Medicare will be under no obligation to cover its approximately $8,000-a-month cost because without an official indication its use is considered “experimental.”
I’m feeling a bit like we’re missing the cart for the horse. In cancer today, the gold standard against which all oncology drugs are judged is whether the drug enables you to live longer, not whether it gives you more months before the cancer starts growing again. But in many metastatic cancers today you aren’t given just one drug and then, when it stops working, told to plan your funeral. You’re simply switched to a different drug.
I know this first hand. My cousin Arlene has been living with metastastic breast cancer for 6 years. Just a decade ago if you’d told oncologists that women like her would routinely live that long after their cancer had metastasized they would have laughed you out of the examining room. Not so today.
I’ve lost track of the number of drugs Arlene has been on in the past six years. When one fails, her doctor puts her on a new one, often one that was just approved or even still in clinical trials, or changes the dose, or adds a different drug. When spots of cancer turned up in her brain, an outpatient laser brain surgery took care of them.
The side effects from her treatments have been minimal — she’s gained some weight, much to her chagrin, and she has a skin rash that makes her very sensitive to the sun. One drug did make her lose her hair, but it’s grown back, and another gave her diarrhea, but that’s over now, too.
Today, she’s doing fabulous.
She hits the gym two or three days a week, travels constantly (Las Vegas, Key West, and Aruba are just a few of the hot spots she and her husband have hit in the past year or two), and she just booked a cruise for February.
So my question is this: Who is to say that those extra “progression-free” months Arlene got from the various drugs she took won’t eventually add up to extended survival?
My point? It’s time we focused on the 800-pound gorilla in the room and found a way to design cancer trials that more accurately reflect what goes on in the real world, not in the rarified world of clinical trials.
If we could do that, then maybe debates like the one we’re having over Avastin will be a thing of the past.
*This blog post was originally published at A Medical Writer's Musings on Medicine, Health Care, and the Writing Life*