Enhancing Cancer Treatment Decisions With Ultrasensitive MRD Testing

Enhancing cancer treatment decisions with ultrasensitive MRD testing

(PODCAST TRANSCRIPT)

Voiceover [00:00:02]:

Welcome to The Results are In from Quest Diagnostics. Conversations with diagnostics industry leaders who enable optimized care pathways for patients.

Jesus Izaguirre-Carbonell [00:00:14]:

Welcome to the Results are In by Quest Diagnostics. I'm your host, Jesus Izaguirre-Carbonell. I'm the director for Medical Science Liaison for Haystack Oncology within Quest Diagnostics. Today we're going to be talking a little bit about minimal residual disease or MRD for short. And we are going to be talking about how this incredible technology does help with treatment management decisions. We're going to be talking about the different clinical settings, including pre-surgical and other settings with this technology can bring utility. And we're also going to be touching into the technical evidence that has been built around all of this technology. In order to do this, I have in here Dr

Jesus Izaguirre-Carbonell [00:00:52]:

Thomas B Slavin, who is the Chief Clinical Officer as well as the Medical Director for Haystack Oncology within Quest Diagnostics. With that, let's get started. The very first thing that I want to do is of course welcome Dr Slavin here to the show.

Dr Thomas B. Slavin [00:01:09]:

Yeah, happy to be here.

Jesus Izaguirre-Carbonell [00:01:11]:

Very nice to have you here. Thank you so much for finding the time today.

Dr Thomas B. Slavin [00:01:14]:

Hey, happy to be here. Thank you so much for having me on again. Yeah. I'm Chief Clinical Officer of Molecular Oncology at Quest. You, you know, that's a lot of words, but essentially it means that I'm helping to bring up the entire molecular oncology portfolio. Most of these tests have to do with complex genetic testing and things called next generation sequencing. And that's really been my background and passion since I graduated medical school many, many, many years ago. I've worked as a clinical geneticist really my whole life.

Dr Thomas B. Slavin [00:01:42]:

So I'm boarded in clinical genetics, also molecular diagnostics and pediatrics. And I've used all that over my life to really do a lot of research and see patients with some element of cancer genetics. And I was at Savio Hope Cancer Center for many years and still have an affiliation with them and help teach on their clinical genomics course. And then I have been a Chief Medical Officer of Myriad Genetics for many years. I was also chief scientific officer of Halo, which is a health system, before coming to Quest. But you know, at Quest, what excited me to come here was really Quest is building an entire molecular oncology portfolio. When people think of Quest, they think of “getting my blood drawn and going to a Quest service center often.” Well, there's no reason we can't also have that blood draw include something around cancer and especially these types of complex tests, even though they're pretty intricate and complex.

Dr Thomas B. Slavin [00:02:37]:

A lot of them are becoming more commoditized over time, meaning that there's not a lot of differences necessarily, and they can be brought up with the infrastructure here at Quest, which is actually extremely sophisticated. And Quest then offers a lot of market access, which I'll talk about a little later, assuming as we go through, you know, some of the benefits here. Yeah. But I'm happy to tell you about minimal residual disease today. I'm the medical director for Haystack, and it's just a phenomenal, fantastic test and was one of the other main reasons I was excited to come to Quest.

Jesus Izaguirre-Carbonell [00:03:08]:

Nice. Thank you so much for sharing all of that. That's a very impressive background. I'm sure everyone here at Quest, we're very happy to have you on board. Okay, so let's jump into a deep dive into minimal residual disease and actually get the episode going. So let's actually go broadly with minimal residual disease. How would you describe MRD for, I guess, someone who is not necessarily familiarized with this technology?

Dr Thomas B. Slavin [00:03:31]:

Yeah. So, you know, minimal residual disease is essentially what it sounds like, looking for very small amounts of disease floating around in someone's bloodstream. At least that's the way it's used today. And there's a lot of different techniques that can be done, but it's really an advanced method that when people think about “how do I figure out what's going on with my cancer”? Oftentimes it's been imaging. We've had some protein biomarkers, but this is really the new frontier and it's absolutely exploded in oncology because it's really real-time tumor sampling. So it's just very exciting. And people are using it now across the care continuum that we'll discuss.

Jesus Izaguirre-Carbonell [00:04:10]:

Nice. Yeah, that sounds like a very exciting technology. So I guess how does it differ from other monitoring methods?

Dr Thomas B. Slavin [00:04:17]:

We discussed briefly some of the others. But I mean, essentially when you're looking at cancer with just, you know, very deep precision in the blood, it does open up new possibilities. And it's.  really a new frontier for medicine and cancer treatment of patients. For instance, imaging, there's obviously many different types of imaging and it has evolved over time. But even advanced imaging, 1 to 2 millimeters is generally about as deep as you can go. I mean, yes, clearly there's some ways you can go a little deeper, but this technology has really been shown to sometimes pick up things even before imaging can pick up pieces of cancer. And that's because it can really come down to the cellular level.

Dr Thomas B. Slavin [00:04:55]:

And look for these essentially just cells floating around and that breakdown products of those cells, which is often DNA. Obviously there's many different ways to do minimal residual disease testing, but the one that's probably become most commonplace at least now over the last few years, is looking at circulating tumor DNA that's floating around and that generally comes from cancer cells that have died over time.

Jesus Izaguirre-Carbonell [00:05:17]:

Wow. Yeah, that's definitely a great improvement. What disease is MRD testing appropriate for and in what settings?

Dr Thomas B. Slavin [00:05:25]:

Yeah, you can use minimal residual disease, really across all kinds of settings with cancer. I think here when we're talking about some of the technology that Haystack offers, which again, I'm the medical director, that's really focused on solid tumors, but all solid tumors. And when we look at the data largely colon, breast and lung are the three main that providers are generally using it for. However, this type of technology can also be used for hematologic disease. And there's different ways to look at that. I think for the purposes here, we'll limit it to solid tumor testing, but it's really just an advancement in the way to look for these cancers. And right now, we're pretty focused on late-stage cancers. And that's been a big push because that's where there's really critical decisions being made about treatment.

Dr Thomas B. Slavin [00:06:08]:

So, you know, do I treat the patient? Do I not treat the patient? How are they responding to therapy? However, when you think of the surveillance setting, yes, for late-stage cancers, obviously you can still use this type of technology, but, you know, I think over time you're going to start seeing it used across all solid tumor stages, including even early stage. Because having a personalized or very sensitive test that can look even at early cancer is just going to be seen as a huge benefit over time because we've gotten really good at cancer treatment over the last few decades and there are plenty of cancer survivors out there. So this is really just an absolute new technology that can be used for surveillance after somebody has had cancer. And yeah, there's going to be benefits across all stages for that.

Jesus Izaguirre-Carbonell [00:06:49]:

Yeah, that's actually very encouraging to hear. In terms of how or what kind of questions does MRD responds? You already kind of like touched on that topic and went over the utility for this technology and surveillance. But what other questions is actually MRD answering?

Dr Thomas B. Slavin [00:07:04]:

Yeah, it's really looking for any traces of minimal residual disease. So is there some sort of ember there after the fire, after the treatment that is indicating that maybe not all the cancer was removed after surgery, for instance.. People get sometimes even pre surgical treatment, what's called neoadjuvant chemotherapy. So you can answer, is that working? Did it work? By looking at these types of blood levels and again, it's real time. So it gives you a sense of ‘is there cancer detected in the blood at this specific time?’ ‘Also on the back end of surgery, was the therapy useful for surgery or radiation?’ But you can use it to monitor patients getting chemotherapy, for instance. And then as I brought up, the surveillance setting is going to be just a very large chunk of the rationale of why people will be using this over time. Because you can really follow then someone long-term and maybe it ends up being every six to 12 months, you're evaluating someone's blood to see if the cancer is coming back in any way.

Jesus Izaguirre-Carbonell [00:08:04]:

Hmm, I see. How about the patients? From the patient perspective, what do you think is the benefit when you are utilizing MRD?

Dr Thomas B. Slavin [00:08:13]:

Yeah, I mean as a patient, it's really that cutting edge cancer detection. I have been fortunate not to have cancer. You know, there are many people obviously with cancer. If I had cancer, I would want the most advanced treatment. As a physician, and advanced treatment and management and decision-making tools. And this is really that it's the ability to give a again real time sampling of what's going on with your tumor. It has a shorter half-life than what's conventionally used for protein biomarkers. So people are depending people's expertise out there.

Dr Thomas B. Slavin [00:08:47]:

But prostate specific antigen like PSA, you have CA125, you have CA15.3CEA. These are very common protein biomarkers that clinicians use to take care of patients and to track cancer. Well, those have long half-lives. I mean, they have seven to 10 day half-life. So sometimes they're just not gonna go up and down quickly. And also the detection sometimes isn't quite as strong as the new tests that are coming out. Like we're talking about, where you can actually look extremely deep in the person's blood with something that has a short half-life, where you can get more to that real time sense of what's going on with the tumor. And also again with a test that's more sensitive than imaging.

Jesus Izaguirre-Carbonell [00:09:26]:

I see. Very, very nice. Thank you for sharing that. Now let's move on a little bit to the next section and talk a little bit about sensitivity. Why do you think sensitivity would matter on MRD testing?

Dr Thomas B. Slavin [00:09:38]:

Yeah, you know, that's really just the nature of improvement. You know, in medicine we're just always trying to get when it comes to diagnostics. We want the most accurate and sensitive diagnostics that are available. We like to innovate as a medical community. And just as an example, I mean you could think about how imaging has translated over time. We started out with radiography and you know, that's still obviously being used today. But it got more and more refined and now you have digital ways to do it. But you think about also in the background of that clinicians and scientists were working on, “are there better ways that we can even do X rays for instance?” So maybe we don't need X rays. Maybe we can do, you know, magnetic resonance imaging like MRIs and maybe we can use PET scans and different things to get lower and lower and lower.

Dr Thomas B. Slavin [00:10:23]:

And there's always new techniques and that whole field continues to improve. It's really been the same on the diagnostic side, at least for blood-based diagnostics. And we've really looked over time at “are there better techniques? are there better markers that we can use to get more of an accurate sense of what's going on with? if I'm specific to oncology here, what's going on with a patient's cancer, maybe CA15, 3 is not the best choice and maybe we should use X or Y or Z. So I think that's really the way we innovate and a lot of research goes into that. So I don't see this really as being any different. So it's different in the sense only that it's now really a novel new technology and that there's just been decades now of research looking at trying to use things like circulating tumor DNA in someone's blood that might be shed from the cancer to inform and you know, that technology has just frankly gotten better over time and it will continue to get better. So but even the commercial tests that are available right now, I mean they are really fantastic and we're seeing things like 6-to-18-month lead times when you look at the literature over on cancer detection sometimes and imaging.

Dr Thomas B. Slavin [00:11:31]:

So I just think it's an incredible exciting time for molecular diagnostics. There's no doubt in my mind that this not only will be the future, but that it's here right now and is accessible for patients.

Jesus Izaguirre-Carbonell [00:11:42]:

Well, all of this is very exciting to hear and just I guess the wheel of knowledge never stop and we are always looking for better or more sensitive things in order to diagnose or to treat patients. That's excellent. Let's talk a little bit into the science, like the data. What evidence is out there supporting MRD testing for treatment management?

Dr Thomas B. Slavin [00:12:06]:

Yeah, as I brought up, there's a lot. Obviously that's been looked at over time on the lead time to imaging and being a minimal residual disease, being a more sensitive diagnostic than sometimes what we could do with imaging. There's lots, lots of publications around clinical validity of this type of test across all kinds of cancers. Really thinking about how it can be used as a prognosis, as you would expect. You know, since this is real-time tumor sampling, if there is tumor floating around in your blood, that's meaningful in some way, and if say you had surgery and now there's tumor floating around your blood, that's generally not a good prognostic sign, meaning that there's a high, high likelihood that your cancer is imminently going to come back. Also, let's say you're on a therapy and you're being followed with circulating tumor DNA because it's such a real-time blood sampling test for cancer. For instance, if your blood levels are not coming down of your tumor while you're on chemotherapy, that very well may mean that your chemotherapy is not working correctly to help kill your cancer cells. So that's the excitement here, that we can use this real-time.

Dr Thomas B. Slavin [00:13:13]:

Other aspects are we have studies now that show that there's chemo benefit. If you have patients that are positive for circulating tumor or these kind of newer advanced minimal residual disease techniques, if you treat them with chemotherapy, you can start getting an understanding of. ‘Yeah, how much benefit did that person get from chemotherapy?’ And that's important as well because that allows us to say in maybe frail patients that can't handle chemotherapy, you can really start quantifying the benefit. “Well, if I don't give the patient chemotherapy and I see circulating tumor floating around in her blood, this is probably what it's going to mean.” And if I do, this is probably what it's going to mean. And then you can have those educated discussions.

Jesus Izaguirre-Carbonell [00:13:50]:

Hmm. So that's actually will be probably part of that benefit that the patients are going to be seeing, like likely being able to adjust the treatment, hopefully being able to remove treatment when it's not needed. I see a lot of benefits definitely coming out.

Dr Thomas B. Slavin [00:14:06]:

Yeah. And there's emerging data and trials going on right now. One of the bigger trials that's been done to date, and it remains the only published trial that's looked at circulating tumor DNA as really an intervention. Specifically in this space has been looking at stage two colon cancer. So stage two colon cancer is a very difficult cancer to know how to treat because very few patients will benefit from chemotherapy. So ideally you want to find the people that are going to benefit from chemotherapy. And there was a study using an early iteration of the Haystack assay that now has moved over to Quest, that looked at patients with stage 2 colorectal cancer and looked at their blood a few weeks after surgery and said, yeah, if they're circulating tumor DNA around, let's give them chemotherapy. If there's not, let's try to withhold chemotherapy and continue to monitor them closely.

Dr Thomas B. Slavin [00:14:56]:

And then let's also just have like a standard of care arm that we can look at. And essentially what that study showed, and this was in the New England Journal of Medicine, it's called the Dynamic Study, it came out in 2022. Essentially it showed that you can give patients roughly about half the chemotherapy, which is pretty impressive. And at the same time, the outcomes are the same. And the five-year outcomes were actually just published in Nature Medicine this year. So pretty exciting. And you can see its final publication. Actually it just came out a few weeks ago.

Dr Thomas B. Slavin [00:15:23]:

So this is like real-time. But there's so many trials going on right now to whether it's adding another chemotherapy to a situation, escalating care, deescalating care using circulating tumor DNA. And it's just so exciting because you can do these with this real- time blood sample type tests and not have to wait on imaging results. So I think it's going to be really exciting. You're also going to see it start coming into just general pharmaceutical trials. I mean it's, it's starting to become much more commonplace. The FDA is looking at the potential to use this over time as data merges as like a surrogate endpoint.

Dr Thomas B. Slavin [00:15:55]:

So maybe we can even use it to speed up clinical trials. But if you think about it, if you start selecting even to compare medication A versus medication B, if you're. Or medication A versus no medication, for instance, watch and wait. Or observation. Having a circulating tumor positive arm, like in a minimal residual disease positive arm of patients, that's an arm of patients that to date we really haven't been able to evaluate. So it gives you a lot of opportunities to now really study a patient population that you know is going to recur and craft some new studies that we just really haven't been able to do this in the past.

Jesus Izaguirre-Carbonell [00:16:29]:

Wow, that's incredible. Half the amount of chemo did definitely. I don't think anyone had heard of anything like this in the past until something like this came out, when it became available.

Dr Thomas B. Slavin [00:16:41]:

Yeah, it's good for patients, good for the health system, you know, good for just the United States medical system and the world's medical system as this technology starts diffusing other countries. So that's really what we want. We want the best care with the least treatment. We want to make sure that when we have cancer that it's cured. And if it's not cured, you know how best to treat it. But if it is cured, one of the goals should be first, do no harm. In medicine, you want to make sure that you're not giving unnecessary treatment.

Jesus Izaguirre-Carbonell [00:17:07]:

Nice. Yeah. Well, perfect. That sounds really, really exciting. The last thing that I want to go over with you is like anything that you believe that we might be forgetting all of the. Is there anything else that you want to bring up?

Dr Thomas B. Slavin [00:17:20]:

Yeah. As I alluded to earlier, one of the exciting things about these tests is just how sensitive they are. However, I will say, even though minimal residual disease can be incredibly sensitive, you could have the best test in the world. But if you don't have a way for patients to get that test, like access for patients, that's a big problem. Also having pathways for insurance, because at the same time, we need to make sure that patients aren't experiencing financial toxicity. And we want to make sure that labs continue to develop these types of tests and they won't do so if there's no avenue for insurance, payment or payment to develop the test. So that's one of the really exciting reasons I came over to Quest is because just the amount of access points and the Patient Service Centers and the mobile phlebotomy services and the ability to work with payers and health systems to really get this testing out into the public and really get it off the grounds. Very exciting.

Dr Thomas B. Slavin [00:18:14]:

So again, the best test in the world does no good if it sits in a laboratory. So you have to get these into the marketplace.

Jesus Izaguirre-Carbonell [00:18:21]:

Very good point. We want people to have access to this kind of test and people to be aware about this kind of test. True. I guess there's multiple things that need to be considered, but the more that this technology is adopted, the more people that gain access to it and can benefit from it. I think we will start seeing more and more incredible stories and evidence coming up. So very, very exciting times. Well, that brings us to the end of today's episode. I want to extend a huge thank you to Dr

Jesus Izaguirre-Carbonell [00:18:48]:

Thomas B. Slavin. This was incredible. Great insights that you could share with us about MRD testing. We did learn about the utilization of this technology in different clinical settings. We touched on surveillance in treatment monitoring and other settings where this technology is bringing amazing changes already. And we actually did a brief overview into the evidence or the scientific evidence out there that is helping driving those changes. Now, if you enjoyed this conversation and you want to stay informed with the latest advancements in diagnostic testing, please make sure that you subscribe to the show and you leave a review.

Jesus Izaguirre-Carbonell [00:19:22]:

You won't want to miss our upcoming episodes where we dive more into groundbreaking research and real-world stories that impact patient care. Thanks a lot for tuning in. I'm Jesus Izaguirre-Carbonell and we'll see you next time at The Results are In by Quest Diagnostics.

Voiceover [00:19:46]

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