The FDA has approved new labeling for the last-chance lung cancer drug Iressa (gefitinib), saying that after Sept. 15 the medicine should be limited only to patients who are already benefiting from its use, the agency announced Friday.
The Food and Drug Administration stopped just short of withdrawing the lung cancer pill Iressa from the market, restricting access to the drug to existing or previous users and to patients in clinical trials.
The action follows the failure of the drug, developed by AstraZeneca, to prolong lives in two clinical trials. This is the first time the F.D.A. has restricted use of a cancer drug that had received so-called accelerated approval.
1. The FDA is saying the medicine should be limited only to patients who are already benefiting from its use. After-all, it IS helping those. Who are those that "benefit" from its us? All the more reason to "test the tumor." Some technologies are already present, some have been available for over fifteen years, some will be out shortly, in that testing. There are three that are so complementary to each other. We are getting a rapidly-expanding list of treatments which are partially effective in a minority of cancer patients, ineffective in a majority of them, remarkably effective in a few, isolated patients, while being enormously expensive. The fastest way to improve things is to match treatment to the patient, like these technologies can and will do.
Gene Expression assays are panels of markers that can predict the likelihood of cancer recurrence in various populations.
Chemosensitivity testing is a test for drug activity against a tumor.
Pharmacogenomic testing is a test to identify patients who are likely to have the most (or least) toxicity.
By testing the gene expression markers of a patient, oncologists can identify those patients unlikely to benefit from adjuvant chemotherapy from those that would. If the patient needs adjuvant chemotherapy, by testing the patient's tumor cells and testing the patient toxicity tolerance, the oncologist can select drugs that have a higher probability of being effective for an individual patient rather than selecting drugs based on the average responses of many patients in large clinical trials.
What a cancer patient would like ideally, is to know whether they would benefit from adjuvant chemotherapy (something gene expression assays may be good at). If so, which active drugs have the highest probability of working (something chemosensitivity testing is very good at) and are relatively non-toxic in a given patient (something pharmacogenomic testing should be good at).
Whether a patient would benefit from adjuvant therapy depends on two things: (1) whether the tumor is "destined" to come back in the first place and (2) whether the tumor is sensitive to drugs which might be used to keep it from coming back.
The gene expression markers (assays) actually can be calibrated to provide information both about the possibility of recurrence and also chemosensitivity. The problem is dissecting one from the other. Studies to date have just looked at whether people had a recurrence.
You can identify gene expression patterns (via assays) which correlate with this. But it can be hard and even impossible to tell what exactly you are measuring: is it intrinsic aggressiveness of the tumor? sensitivity to adriamycin? sensitivity to cyclophosphamide? sensitivity to iressa? sensitivity to tamoxifen? You find a gene expression panel which correlates with something, but picking apart the pieces is hard.
You can begin to do this if you combine gene expression studies with cell culture studies. Use the cell culture as the gold standard to define the difference between sensitivity and resistance. Then see which pattern correlates with which for individual tumors and individual drugs. It can theoretically be done (and certainly will be done, over time), but it's not easy.
And then you come to the 1,000 pound gorilla of a question: What effect will the different individual drugs have in combination in different, individual tumors? This is where cell culture assays will always be able to provide uniquely valuable information. But it's not one versus the other. The best thing is to combine these different tests in ways which make the most sense. One month's worth of herceptin + avastin costs $8000. That's without any docetaxel and blood cell growth factors and anti-emetics. If nothing else, we can't afford too much trial and error treatment.
Iressa is synergistic, but one needs to test the tumor to see which cancer patients fit the bill.
Posted at 3:40PM on Jun 20th 2005 by Gregory D. Pawelski