Diagnosis and Treatment of mCRC With a Focus on HER2-Positive Disease: Year in Review 2022 - Episode 2

Role of ctDNA and MRD in Identifying and Managing Metastatic CRC

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Shared insight on the optimal use of circulating tumor DNA and minimal residual disease in the identification and management of metastatic colorectal cancer.

Cathy Eng, MD:
Jaclyn, do you want to comment briefly on circulating tumor DNA. It's such a hot topic right now and what are your thoughts regarding circulating tumor DNA? And as well as the tumor agnostic versus tumor-informed panels that are available?

Jaclyn F. Hechtman, MD: The meaning of circulating-free DNA in solid tumors at this point are early detection and minimal residual disease detection. And the use of cfDNA for solid tumors, it's still in its infancy for colon cancers. There have been trials which examined the utility of additional therapy if minimal residual disease is detected by cfDNA testing after curative intense surgery like stage 2 or 3. If the patients still have cfDNA positive so you do that and if it's still positive, then these trials – they're still trials. It's not standard of care. We'll go ahead and see if additional therapy for that patient would help compared to an arm that doesn't do that. And then also cfDNA may be also used to track a biomarker during target therapy trials where they have looked on the side to see if HER2 levels fluctuate and see if cfDNA during HER2 inhibitor. From my intake it's still in its infancy and it's not standard of care yet. I'm not sure what you guys think of that.

Cathy Eng, MD: I was just about to ask, get the input of Dr Saab and Dr Ciombor. We encounter this discussion a lot. There's a lot of interest from patient advocates. It's a lot in the press now regarding, for instance, the DYNAMIC trial. What are your thoughts moving forward for our patients regarding the role circulating tumor DNA and molecular testing in general? Here we're talking about a rare patient population for some of our patients especially regarding HER2. What do you view as the role of molecular testing in circulating tumor DNA? And what are barriers that you're encountering in your practices? Kristen, would you like to go first?

Kristen K. Ciombor, MD: Yes. You brought up a great point, and circulating tumor DNA, we're anxious to use it, but we have to be cautious because there are some limitations to the technology, for sure. As you mentioned, the DYNAMIC study presented this year at ASCO [American Society of Clinical Oncology] with a recent updated ESMO [European Society for Medical Oncology]. And then from our Japanese colleagues, the GALAXY observational cohort of the circulate, Japan. What we know is that circulating tumor DNA, particularly as it stands for MRD, is very prognostic, we know that the patients who do have positive ctDNA, particularly after the completion of definitive therapy, do poorly and these are the patients we want to be able to treat differently. The problem is, we don't know if our assays yet are sensitive enough and, in some ways, and in some tumor stages and sites of recurrence the sensitivity is lacking a bit. And we also need to know that if we utilize the ctDNA information that we can impact the patient outcomes, and that's what we're lacking right now. But we will get the information. We have multiple ongoing studies that are very well designed, and we need to wait for those results to know how to move this forward as standard of care.

Tanios S. Bekaii-Saab, MD: I totally agree with Kristen. We have to separate the circulating tumor DNA that discussion that we typically associate with the utilization of molecular target therapies in the more advanced setting versus the minimal residual disease assessment in the earlier stages or even in all metastatic disease. There has been blurring of the lines in the discussion. Everything has been called circulating tumor DNA. That has become a bit confusing to the practitioner, I would encourage to go back to saying to the discussion where circulating tumor DNA is essentially meant to what it's meant as part of next-generation sequencing or genomic assessment versus assessing minimal residual disease or even assessment of response. And as Kristen said, those are not primed for use yet. They selectively maybe but I wouldn't do it indiscriminately. Regarding your circulating tumor DNA, it has become very useful in our practice. Tissue is an issue. Many times, it takes time. A lot of the studies do require molecular characterization. I know we're going to talk about clinical decision-making dependent on having access to this genomic data before initiating certain therapies and overall, it has become a very useful adjunct to tissue sequencing with results coming back in 7 to 8 days.

Cathy Eng, MD: Thank you so much for discussing that, and I'm so glad that we brought that up because as you mentioned, the terminology can be confusing to many providers as well as patients.

Transcript edited for clarity.