OncologyTube: [00:00:00] Okay. We’re here at ASCO GI 2024. And, we have the honor of, having Dr. Christopher Lieu, MD medical doctor, associate director for clinical research, co director gastrointestinal medical oncology at University of Colorado and Aurora, Colorado. Dr. Lu, thank you so much for joining us. Well, thank you for having me.
Okay, today we’ll be discussing the NRG-GI008 colon adjuvant chemotherapy based on evaluation of a residual disease otherwise known as the circulate North America trial, which is featured here at ASCO GI 2024. So Dr. Liu, can you provide an overview of the NRG G. I.
Christopher Lieu, MD: 008 study. Yeah, it’s a very long title, right?
the purpose of circulate North America or NRG-GI008 is to try and figure out if we can utilize a technology called circulating tumor DNA to guide the management of [00:01:00] patients with early stage colon cancer. So circulate North America allows patients with high risk stage two or any stage three colon cancer that has been surgically resected to have C.
T. D. N. A. Testing. ctDNA Testing looks for something called the presence of minimal or molecular residual disease. Why this is important is because patients with no evidence of ctDNA In other words, no evidence of molecular or minimal residual disease of cancer likely have a much lower rate of recurrence compared to patients who have persistently positive ctDNA.
So in this study, patients with surgically resected stage 2, high risk stage 2 or stage 3 colon cancer will have the ctDNA testing done. If ctDNA testing is negative, in other words, it’s not present, patients are randomized to receive standard of care chemotherapy, which is what patients almost, you know, essentially always are recommended to have in that setting, or randomized to receive surveillance.
with the typical surveillance that we [00:02:00] do for early stage colon cancer, but with ctDNA testing as well. If patients are positive post operatively for ctDNA, then they then get randomized to standard of care chemotherapy or an escalation of chemotherapy with a triplet regimen that we call Fulfironox. If patients who are ctDNA negative turn positive over the course of their surveillance period, then they also get randomized to receive.
standard of care chemotherapy or triplet chemotherapy. The purpose of this study is really to try and find out can we use this type of testing to determine who should and who should not receive chemotherapy, as well as could an escalation of chemotherapy in our highest risk patients really lead to, improved outcomes.
Fantastic.
OncologyTube: Thank you for that overview. many of our viewers are oncologists and hematologists. So, how significant is the potential of ctDNA status as a biomarker for determining the need for adjuvant [00:03:00] chemotherapy in resected colon cancer patients and how might it improve the risk stratification process compared to traditional clinical and
Christopher Lieu, MD: pathological features?
Yeah. So, you know, when it comes to ctDNA, we have Few randomized trials, but we’re getting more and more what we call observational data, and that is data that we can kind of observe by looking at a cohort of patients. What we know from the observational data is that patients who are ctDNA negative or ctDNA positive, that is incredibly prognostic.
Patients that are persistently ctDNA negative have an extraordinarily low rate of recurrence. Patients who are ctDNA positive and remain positive have an extraordinarily high rate of recurrence. So we know already. That ctDNA is a better predictor of recurrence than a lot of the clinical features that we look at, lymph node status, size of the tumor, depth of invasion of the tumor.
So those things are pretty well established. What do we really want to know as providers? We want to know if we can use this test to [00:04:00] select patients for chemotherapy or potentially for observation, because we want to know what percentage of the patients or what proportion of the patients are cured with surgery alone, who do not need chemotherapy, but as providers, we’re just recommending everybody to get chemotherapy anyway.
And that’s where the randomized trials are really, really important. And this is where we’re going to see the field really move over the next couple of years as these randomized trials like Circulate North America and NRGI008, as they begin to report out. But we’ll have a better sense of how effectively we can use this test to determine who should get chemotherapy, who does not need chemotherapy, or potentially who needs some, something beyond chemotherapy to treat their cancer.
Excellent.
OncologyTube: Okay. Can you explain the rationale behind the decision to randomize resected colon cancer patients into different treatment arms based on their CT DNA status, and what are the Yeah, and you know, it’s really a simple [00:05:00] question,
Christopher Lieu, MD: right? If you’re ctDNA negative, the hope or the thought is that they’re potentially cured with surgery alone.
And so really what you’re trying to kind of figure out is do those patients really need chemotherapy? And how great would the answer be if we could select the patients who don’t need chemotherapy to not receive chemotherapy? Then we’re not harming them, right, with a toxic agent. So I think that that’s really just the power or what we’re kind of hoping for in the ctDNA negative group.
But obviously we need that randomized clinical trial data to know whether that hypothesis is correct. For patients with ctDNA positive, right, disease, you know, chemotherapy we know has a rate of clearing ctDNA and that’s really, really promising. We know that from the observational data. I think the real question is can we improve the odds of eradicating that disease?
with more aggressive chemotherapy. we don’t know the answer to that. And so, you know, obviously, we’re hoping that the answer is yes, that we can [00:06:00] be more effective in treating this high, high, high risk population. But again, that’s why we need the clinical trial data.
OncologyTube: What challenges and considerations should be addressed when implementing ctDNA monitoring in clinical practice for resected colon cancer patients, and how might this approach impact treatment decisions and the patient outcomes in the future.
Yeah,
Christopher Lieu, MD: I think right now the CT DNA landscape is, you know, we’re getting more and more information, but it’s still very, very confusing, right? How do we use the test? should we be offering this test to, you know, what group of patients? And I think that those are all things that we can’t truly answer at this time.
And then not only should we get the test, but it’s just the logistics of even obtaining the test. There are tumor informed assays, which require submission of tumor tissue. There are plasma based assays, which do not require pathology to send tissue to a third party or or another location. The turnaround times are better for plasma based testing compared to [00:07:00] tumor informed testing.
But as practitioners, we believe that tumor informed testing is more sensitive than plasma based testing. So these are all the kind of complex things that we’re just now starting to kind of not only figure out the importance of, but even the logistics of that testing as well.
OncologyTube: All right. This has been an interview with Dr.
Christopher Lieu, MD a medical doctor, associate director for clinical research, co director gastrointestinal medical oncology at University of Colorado in Aurora, Colorado. Thank you so much for joining us.
Christopher Lieu, MD: Thank you for having me.