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Supplements Exploring the Evolving Landscape of Precision Medicine

The Pharmacogenomic View of Precision Medicine: A Q&A With Howard McLeod, PharmD

As we look at our value, we use personalized medicine to try to optimize quality and to at least justify, if not reduce, cost. It could be that a cost is what it needs to be, but at least we know it is on purpose. It could be that the patients are going to get toxicity, but at least we know that ahead of time and can be ready to manage it. It is a lot cheaper to manage grade 1 toxicity, very mild toxicity, than it is to manage the severe toxicity that requires hospitalization. We have been using this to think about how we manage patients. If we are going to be managing these patients, let’s look at it in a holistic fashion. Let’s try to reduce things, try to take the things that have been assumed to be part of practice and really question them. Can we reduce the severity, if not incidence, of neuropathy? Part of it has just been a way of changing the culture of our institution, which has been an early-adopter institution to begin with, to really take this on as being normal.

AJMC®: How might the evidence-based personalized medicine pathways of care developed at Moffitt Cancer Center be translated and communicated to other treatment centers?

McLeod: We did develop internal versions of pathways. Our pathways are a little bit unique in that they manage the patient’s care, so there are things around surgery choices, radiation choices, chemotherapy choices, imaging choices, endoscopies, and all the ways the patient is managed. It allows us to come to a consensus as a group. If there are 4 ways to treat something, those 4 ways will be on the pathway. Anything off the pathway would be quickly identified, and we can either adjust the pathway if there’s new data or try to understand what’s going on. Insurance companies want to reduce variability, and we can talk to them about our strategy in terms of developing consensus pathways and going forward. It’s not just guidelines or  suggestions but rather trying to make a more objective decision and then follow up on it. Our pathways right now are available through being licensed, but they are not available for free. There are a number of institutions that have licensed some or all the pathways. It is a lot of work to keep them up, but it has become part of our payer strategy. It has become part of the way we help our community partners practice better. If you are going to have a Moffitt sticker on the door, you are also buying into practicing within the pathways. You have to have a good reason to not practice on pathway. We also build in the molecular sides and try to be as comprehensive as possible. 

AJMC®: How do you think biomarkers will increasingly become the standards for treatment selection and treatment in cancers in general, rather than anatomical and other traditional ways of staging cancers?

McLeod: I think for surgery and for radiation, anatomy will always matter. For systemic chemotherapy, it will be a long time before we get rid of anatomy in our description. It is going to be hard not to call a cancer rising from the breast a “breast cancer.” But in terms of the way we treat it, it is already starting to change. As we understand the molecular drivers, we cannot help wanting to respond to them. That has caused a change in our structure—a change in the way tissue is handled, prioritizing certain markers versus others. If you have metastatic carcinoma, and you have only a brushing or something where you have very few cells, you could make the argument that it is more important to know the molecular drivers than it is the diagnosis. It is rare that we don’t have the diagnosis, but from a tissue priority standpoint, knowing what to treat becomes more irrelevant. We are not trying to figure out if it is a breast cancer metastatic to the liver, or a colon cancer metastatic to the liver—we have tissue from the liver cancer that has abnormalities that we can target. And suddenly there is less of a need to know the anatomical origin. We do still try to find that, but you can see the change that’s happening with systemic therapy; we want to know what’s driving it and how to stop it. It’s almost trivial to know where it came from because it’s less and less part of the decision on how to treat it.

AJMC®: Where do you see precision medicine going in the future? We’re seeing the most use of precision medicine and personalized medicine with cancer now, but where might the next frontier be? Or will it continue to be cancer for the foreseeable future?

What are some of the growths that you’ve seen in precision medicine, and how do you see that projecting out over time?

McLeod: There are a couple of areas in which we are seeing a lot of activity in terms of precision medicine. One is in mental health—both at the family medicine level and the psychiatry level. It is more for depression than schizophrenia, but there is activity in both. A lot of patients now get a DNA analysis done for drug metabolism pharmacogenomics prior to the choice of antidepressants. That is definitely an emerging area.

Another area is organ transplantation. Prior to transplant, the transplant surgeons want to know information about both the patient and, when possible, about the donor, to be able to choose the type and dose of immunosuppressant therapy.

There is activity in cardiology, but not necessarily a lot outside cardiac catheterization labs. There are pharmacogenomics going on in the cardiac catheterization lab at many centers, but in terms of treating high blood pressure and heart failure and such, there’s not a lot of pharmacogenomics happening currently.

Precision medicine is also emerging in the use of general anesthesia—not for the anesthetic but rather for things like the anti-vomiting medicine. Anesthesiologists don’t like risk. They worry about a 1 in 1000 or a 1 in 10,000 event. They’re not interested in any patients being at risk for aspiration pneumonia because they vomited while they were still under anesthesia, so there is activity going on in that space to try to choose therapy accordingly. And that affects many different types of patients; surgical patients are usually the largest volume of patients in a hospital. Overall, we are starting to see a lot more activity happening with precision medicine.

AJMC®: What do you see happening in the next 5 to 10 years in personalized medicine?

McLeod: In the next 5 years or so, I think a lot of it will be focused around which drug and which dose. Also, expanding on what is already going on further. During the next 5 years and beyond, we are going to see more emphasis on what it is the patient has. And what I mean by that is, “What does high blood pressure mean?” It probably means 20 different things, but right now we just think of it as 1. So as we start getting information, whether it’s a biomarker or genetic test, we can now start treating patients accordingly. The same thing applies with depression and other common diseases. There are some areas, like infectious disease, where currently we have a large therapeutic index; we can overdose the patient and it doesn’t harm them, but it will kill the bugs. However, as we get more resistance, we are going to start to see more molecular studies there. We will also see more rapid diagnosis through molecular testing. Right now, a well-equipped emergency room can diagnose viral meningitis in 2 hours with a molecular test, whereas the rest of the country will either never diagnose it or will take days to diagnose. We are starting to see rapid turnaround assays for sepsis and other areas that will allow us to make more informed decisions. I think the bottom line is knowing more about the patient and their likely response to treatment and trying to make sure that that happens in a uniform fashion. Informatics is also going to become more important because there’s going to be so much data. All of this in the backdrop of an insufficient number of physicians and other health professionals being trained, so it is going to be a really interesting next decade.

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