Neuro-oncologist at the Huntsman Cancer Institute, Joe Mendez, MD, talks about how precision medicine is changing the medical field.
Interview conducted by Ivanhoe Broadcast News in 2023.
Let’s talk about precision medicine. What does that mean?
Mendez: I like to think about precision medicine as really this idea of tailoring the medication or the treatment to the patient’s tumor. Precision and personalized medicine in a sense go together to some degree. And so I like to think about it as a treatment that’s really designed not for every type of cancer, but specifically a treatment that’s designed for specific tumor type.
How many different brain tumor types are there?
Mendez: There’s quite a few different brain tumor types. So that’s where the beauty of precision medicine can be very helpful, is that each of the tumors, not every or not all of them, but some of them have unique genetic characteristics of those tumors, genetic changes that is, that are thought to potentially be leading it to behave like a cancer. And if we use targeted therapies, i.e., precision medicine, to attack those tumors, the hope is that’s in a sense, better.
Why would it be better?
Mendez: It could be better in the sense that it’s, again, more tailored. So specifically going after a specific component or a genetic change in that tumor that is making it behave like a cancer. The side effect profiles can be different. It’s not necessarily that they’re less toxic, it’s just that they’re different. They still can be very toxic therapies as well. But it is a unique way of attacking cancer, something that we haven’t done for a long time, and so this is really part of the new frontier so to speak of treating cancers.
Before it was just one-size-fits-all treatment?
Mendez: Yes.
And talk to me about why it’s better to do it, though you did touch on that little.
Mendez: When you think about classic treatments meaning chemotherapies for cancer, those drugs are really designed to inhibit or affect the way that a cell divides, i.e., the cancer cell. The reality is all cells in our body divide and so that’s why those therapies can be so toxic, because normal cells are being attacked. When you look at precision medicine and they are using targeted therapies, i.e., those therapies that are designed to attack a change in that cancer, a genetic change in that cancer. Those therapies, again, are going to only impact, and for the most part, those cells that actually have that genetic change or alteration.
So, let’s say, in the case of David Perry, why was he a good candidate for this, what was the name of that inhibitor?
Mendez: It’s called Vorasidenib. It’s an IDH inhibitor.
Why was he a good candidate?
Mendez: Well, one reason why he was a good candidate was because of the clinical trial, the way it was designed was specifically to look at patients like him. So the key thing there was that his tumor is known to have an IDH mutation, and that’s isocitrate dehydrogenase. So that’s a characteristic alteration or change in the tumor and it’s thought to be an early change in the tumor that leads it to behaving cancerous.
So, he was saying the first time around it was non-placebo. So, his tumor continued to grow. The second time it’s like it stopped growing, is that right?
Mendez: Correct.
Can you talk about that?
Mendez: So the way that the trial was designed is because it’s a Phase 3, patients were randomized to either receive a placebo, a sugar pill, or to receive the active drug, which is the Vorasidenib of the IDH inhibitor. And of course, every patient wants to receive the active drug because that’s the drug that we hoped would help patients. In this trial they were blinded. So no one knew what the patients were receiving. So if they progressed on the treatment they were receiving at the time, we would unblind them, which means we would reveal whether they were getting placebo or getting the active drug. In David’s case, the first time he was receiving placebo. The clinical trial allowed for what we call a crossover. It’s just a technical term for when a patient is receiving the placebo, they can choose to move into and receive the active drug, which is what he chose to do and since the time he’s been on the active drug he’s had control of his tumor since then.
So, in the time that it grew he simply doesn’t really have any sight of the tumor. Is that normal, is it unusual or again, it’s just unique to him or everything different?
Mendez: It’s a good question. So in general, part of the reason the beauty of this clinical trial is it’s designed for low-grade brain tumors, so Grade 2 tumors. These tumors typically grow very slowly. So this trial in a sense was nicely chosen in the sense that we can allow these tumors to grow potentially and typically not have significant impacts on the patient because that growth is relatively slow. So these tumors are not necessarily aggressive. The way that the eligibility criterias outlined these tumors, we chose patients who we thought would be safe to participate in a trial and potentially get a placebo. A lot of symptoms that are related to tumor growth really honestly are dependent upon where the tumor is located in the brain, and so certain patients may have lower or higher risk of that depending on where their tumor is located.
Where was his located?
Mendez: I think he’s a left frontal, if I remember correctly.
So, that also does determine him being a not safe, but like- does that also go into the decision to put them in the trials?
Mendez: No, really, it’s just about how the patient is doing at that time. And so patients had to be a certain functional status to clinically participate. It doesn’t mean they had to be normal so to speak. They could have neurological deficits, but they had to be a certain level of function and able to participate.
How much did him being in such good shape impact how he’s doing?
Mendez: There’s no question that David’s, I would say, physical activity has positively impacted him. I think part of that beauty is we think a lot of age can help and be a contribution, meaning the younger you are, typically, the better patients can do. How physically active they are. David is a good example of that. And so I think- and the way that I think about it is just any of the potential things that could contribute to making it more challenging to tolerate a treatment that you don’t experience is going to make that treatment much more easy to tolerate and that would likely result, we would hope, in better outcomes as well.
So, for him, with the tumor that has stopped growing, but I don’t know if you can tell the future will be for him that will this be a drug he’s on for the rest of his life or we have to go back for surgery?
Mendez: It’s good question. So those are questions we don’t actually know. From what we know from the data that was published in New England Journal Medicine, these tumors eventually all grew. So really, the data, what it shows is that this drug appears to help patients. So the time of which the patients were randomized to receive either a placebo or the active drug, to the time at which their tumor grew to 25% or they had clinical progression, that time was significantly extended for patients who were receiving the active drug. So those numbers were close to 11 months of control of their tumor on placebo to around I think it’s 27.7 months in the patients who are receiving the active drug.
I get surprised of the study, but just, we’ve seen how they respond to it. He said he didn’t have any side effects?
Mendez: In general, I think the drug is incredibly well-tolerated. And so that’s the other real benefit to the clinical trial. I would say is obviously the positive results meaning it helps patients. But furthermore, it’s a therapy that’s tolerable. So David was able to live a fairly normal life even though he’s on active treatment, which is obviously an ideal scenario and doesn’t always happen in the world of cancer.
And that just takes a pill?
Mendez: Yeah.
So would he have had to go through chemo or radiation?
Mendez: David is one of those patients who eventually who will require unfortunately chemo and radiation. This drug is designed to hopefully delay that. And that’s what the data really shows, is that the ability to control the tumor for X number of months longer would result in, of course, delaying his exposure to chemo and radiation, which are all very toxic treatments that can have more delayed side effects including cognitive changes. And so anytime we can delay those more aggressive therapies, I think it’s definitely a win for the patients.
So, with precision medicine, is that something, I guess, we’re going to see in all aspects of care?
Mendez: I think it’s a really good question. The way that we think about precision medicine unfortunately, there are going to be inherent biological things or attributes of tumors that may not make it amenable to being applied to every patient who has cancer. The goal is, of course, from a science perspective, to understand the molecular underpinnings or the changes in these tumors that lead them to behave aggressively. The challenges is there’s not always a drug for a specific type of change or alteration in these tumors for every patient’s tumor. That change may not be the only change, which of course, if you have a bunch of these changes in a tumor you could imagine that trying to attack only one change may not result in a very positive impact. But I think really the goal is to understand what are the potentials for these drugs, which tumor types, and trying to get as much benefit as we can from these types of therapies.
END OF INTERVIEW
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