The FDA’s decision late Friday afternoon to provide “accelerated approval” for the use of Avastin in the first line treatment of HER-2 negative metastatic breast cancer was the culmination of a lot of handwringing and head scratching on the part of many people.
From my vantage point, the FDA made the right decision in a difficult situation. That said, this is not the end of this story.
I have previously written about Avastin and the decision of an FDA advisory panel several months ago to (closely) vote not to approve the drug for this indication.
That decision by the panel members had to be a difficult one. Metastatic breast cancer is a disease that is treatable, but not considered curable. Every time we have a new drug that may offer benefit to women in this circumstance, it is important that we make certain that we are providing an effective therapy that will indeed help those in need.
The Avastin situation is of interest for a number of reasons.
When determining if new cancer drugs are effective, the FDA generally wants to see evidence that the group treated with the drug lives longer than the group that receives the standard therapy. In this case, Avastin was added to the chemotherapy drug Taxol, a well established and effective drug in the treatment of metastatic breast cancer.
Unfortunately, based on the data available at the time of the panel review, Avastin did not improve survival of the women who received it to an acceptable degree.
What it did do was double the time until the disease progressed from 5.8 months in the women who received only Taxol, to 11.3 months in the women who received Avastin in addition to Taxol.
Nagging questions remained when the FDA advisory panel had to make its recommendation.
For example, it may have taken longer for the disease to progress with Avastin treatment, but were the women better off during that time? There was no evidence presented which objectively supported that their quality of life had improved.
That said, most oncologists either in their own experience with Avastin (it has been used “off label” by oncologists pending the FDA review) or their experience in similar circumstances found it hard to accept that delayed progression would not be associated with an improvement in function and quality of life. However, the data wasn’t available to support that opinion, and we have learned all too frequently recently that expert opinion may not equate with objective facts.
The other issue was that there were more serious side effects seen in the women taking Avastin compared to those who received the standard chemotherapy alone.
All of that information considered, I did note in my December blog—popular commentary to the contrary—that there had been other biologic drug approvals recently based on increasing the time to progression, and not limited solely to improved survival. The approval of Tarceva in the treatment of women with HER-2 positive metastatic breast cancer was such an example.
So, as I mentioned above, in my opinion the FDA on Friday did the right thing by granting this conditional approval.
There is still more work and analysis to be done. As noted in a Genentech (the company that makes Avastin) press release,http://www.gene.com/gene/news/press-releases/display.do?method=detail&id=11027 the company has agreed to provide the FDA with data from ongoing trials. The company wrote that review of this data—which is expected to be available by late 2008—will be needed before this accelerated approval can be converted into a full approval. (Interestingly, I cannot find an announcement on the FDA website at the time I wrote this Monday morning.)
Before everyone celebrates, however, we must remember what happened with another targeted therapy called Iressa, which was initially approved by the FDA in 2003 for the treatment of lung cancer.
That drug also had a secondary review, and based on additional study findings, the FDA had it removed from the market in 2005. Although the Genentech data is promising, there is no guarantee that the same thing could not happen here.
But the alternative of not approving Avastin, in my personal opinion, would have created a worse situation.
Avastin in the treatment of metastatic breast cancer is not inexpensive. Had the drug not been approved, I would not have been surprised if insurers vigorously opposed its off-label use or made the co-pays so onerous that only the wealthy could have afforded it (there is no guarantee that that won’t happen under the current scenario with approval).
In its press release, Genentech did indicate that it will provide Avastin free of charge to any woman who exceeds 10,000 mg of the drug in a 12 month period. They go on to say that the cost for 10,000 mg is approximately $55,000 wholesale. Given mark-ups at the retail level, one can’t get past the fact that this is an expensive drug—as are many other new, targeted therapies.
As a point of reference, the dose of Avastin in the clinical trial was 10 m/kg on days 1 and 15 of each course. For a “typical” 154 pound/70 kg woman, that would translate to roughly 1400 mg of Avastin per 4 weeks. The 10,000 mg “mark” would be reached about 7 months into treatment (28.6 weeks, to be exact).
Medicare Part B (fee for service) currently allows $57.46 for 10mg of Avastin. The cost for our “typical” patient $57460 at Medicare rates before the free medication offer would be available. Medicare covers 80% of the drug’s cost under Medicare Part B. With a 20% co-pay for drugs administered under Medicare part B, that would translate into an out-of-pocket cost for the drug in the amount of $11,492, not considering benefits available if a patient had co-insurance to help cover the costs.
What we have here is a confluence of circumstances that point out several of the difficult issues we must face as patients, oncologists and as a country.
First, the approval of Avastin in the treatment of HER-2 negative metastatic breast cancer does appear--based on the current evidence--to be a significant step forward. We hope that the additional trial data will support and expand the benefits of this truly remarkable drug. At the same time, we must reserve some caution that this drug can have serious side effects, and it is important for patients and their doctors to have full, open and honest communications about the benefits and risks of the therapy.
Second, we have to develop clear and understandable guidelines for clinical trials in cancer treatment so that we don’t continue to run into these situations with the FDA where we must make what I call “Solomonic” decisions based on less that than the best evidence. Avastin in breast cancer is but one example of the controversies surrounding the drug approval process that must be resolved going forward.
Third, we can’t ignore the fact that many of our new cancer treatments are very expensive. Without affordable access to care, we are going to create a multi-tier system of medical care with the best care available to a few and a lower standard available to everyone else.
The American Cancer Society has declared its position on affordable, accessible health care as a key in moving our efforts forward to diminish the burden and suffering from cancer. Breakthrough drugs and new indications for those drugs highlight how important it is that we address access to care now, before we suffer the consequences of our inactions.
In the meantime, thousands of women will hopefully benefit for this treatment, and that is something we should all celebrate.
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