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Predictive Testing for Chemotherapy Responsiveness

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GCVL_LU-B12_Predictive_Testing_Chemotherapy_Responsiveness

 

Dr. Nathan Pennell, Cleveland Clinic, evaluates chemotherapy sensitivity assays, describing the difficulties inherent in predicting response to chemotherapy agents.

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I’d like to talk to you now about assays for testing for sensitivity to chemotherapy, or chemotherapy sensitivity assays. These are very simple and make perfect sense — you take a biopsy of a patient’s cancer, and do a test on it to determine what the best available personalized treatment would be, and then you tailor the patient’s treatment to that biopsy. This has been the gold standard in what we’ve been trying to do for decades, in all types of cancer, and we are already doing that in lung cancer where we’re looking for driver mutations such as EGFR mutations or ALK gene fusions, and then tailoring treatment based upon the presence of those mutations.

But what about chemotherapy? It’s still the backbone for most lung cancer patients — can we use an assay to tell which is the best chemotherapy that a patient might respond to? Well, the short answer is probably not, but let me explain why: there are two different ways to do this. One is to do specific tests or stains on the biopsy material for different markers that might predict whether chemotherapy would work or would not work, and the ones that are best known are called ERCC1 for platinum drug sensitivity, RRM1 for Gemzar sensitivity, or thymidylate synthase or TS for Alimta sensitivity. Studies have shown that different levels of these markers do tend to correlate with whether patients respond to these drugs. The problem with using these is, they’ve actually tried this in clinical trials, where some patients are treated with chemotherapy tailored to their different pattern of stains, and some people just get standard chemotherapy, and in the end, people all did about the same — chemotherapy worked just as well whether you did it based on these predictive markers, or whether you just picked it based upon the best available evidence for chemotherapy for that type of cancer.

So right now I would not recommend using that type of assay to determine a particular chemotherapy agent, despite the fact that companies right now will do this test and can send you a report with recommendations.

The other type of assay that’s done, which I think is more interesting, is they take a living bit of cancer out of the patient’s tumor, and actually grow it in a dish to treat those living cells with chemotherapy and see whether it works or not. The other way is to take living cancer and put it in a mouse and create a tumor in a mouse, what’s known as a xenograft, where we essentially create a little living model of your tumor, and you can treat the mouse with chemotherapy and see which ones work best. It’s very elegant, it’s very exciting.

The problem is, it’s expensive, it’s technically difficult, and it can take a long time and not work for a lot of people. The other problem is, the minute that you remove a cancer from a patient and put it in a dish, that cancer changes dramatically. It really doesn’t behave the same anymore, the way it did when it was in a person. It might be a little more accurate in a mouse, but even then, you can’t really trust that it’s going to behave the same way, and so as of right now, we really don’t have enough evidence that using these types of assays really will predict what’s going to happen in a real patient, and practically speaking it’s not going to be something that’s likely to be helpful in time for a patient who needs a choice right then.

The other thing to keep in mind is, lung cancer really doesn’t have a lot of differential sensitivity to different chemotherapies. What we tend to find in the clinic is that, tumors that are sensitive to chemotherapy often respond to many different types of chemotherapy; tumors that are resistant to chemotherapy are often resistant to all types of chemotherapy. You really don’t see that much differential activity from one agent to the next, so even if you get a report that predicts one better than the other, the likelihood is that it’s not going to do much better than just picking the best available proven chemotherapy.

So, in 2015, I would say don’t waste your money on these assays, but hopefully we will continue to investigate it and eventually that will change.


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