Circulating Tumor DNA in Gastrointestinal Malignancies

Suneel Kamath, MD, Taussig Cancer Institute at Cleveland Clinic, Cleveland, OH, gives an overview of his talk on circulating tumor DNA (ctDNA) at the 2023 Great Debates and Updates in Gastrointestinal Malignancies meeting in Chicago, IL.

Transcript:

Hi, I'm Dr. Suneel Kamath. I'm a GI medical oncologist from the Cleveland Clinic Taussig Cancer Institute. I spoke today at the Great Debates and Updates in GI Malignancies meeting on ctDNA testing in GI cancers. This has been a really exciting technology that's been developed first in colorectal cancer, but it is making its way into other GI cancers as well.

The most exciting thing we've seen so far is data from the DYNAMIC study showing that in stage 2 colon cancer we can safely avoid giving chemotherapy to a number of patients that are ctDNA-negative, and we can select better for people who truly need platinum-based chemotherapy. What they showed in the study was that those who are ctDNA-positive are more likely to get oxaliplatin-based chemotherapy, but that also seemed to translate to better recurrence-free survival as well.

We also have data now from the GALAXY trial, which looked at stages 2 through 4 colorectal cancer, looking at ctDNA-guided management for patients who undergo curative surgery. What that showed was that, as we've seen in other studies, that those who are ctDNA-positive after surgery have an extremely high risk of recurrence. But what was really interesting is we found that patients who had received chemotherapy in that setting were able to clear that ctDNA at a very high rate. 70% of those patients were able to clear that and that translated extremely well with an improved recurrence-free survival, which that really is quite novel finding. We've seen for a long time that ctDNA is prognostic, that this is a first really high quality evidence I would say that shows us that giving more chemotherapy in that setting can actually change that outcome and improve survival for our patients.

There's a lot still to come in the advanced setting as well. EGFR inhibition has been a really interesting story in the last few years in colorectal cancer. We have found by using ctDNA to properly select patients who have a certain genomic profile, the absence of RAS, BRAF mutations, HER2 mutations, the lack of EGFR extracellular domain mutations as well. If you select the right population, you can really find people that are going to benefit very strongly from EGFR inhibitors versus with bevacizumab.

We also have data showing that by using the same genomic signature, if you select for the right people, you can actually re-challenge with EGFR-inhibitors as a single agent and still see great responses in people that are highly treatment refractory. Really great tool to have for people who are going to be difficult to treat with chemotherapy.

In other GI cancers, the data's still very much evolving, but there's some really good evidence in both pancreatic cancer and gastroesophageal cancers as well showing that those who have ctDNA positivity after neoadjuvant chemotherapy are going to do very poorly, going to have a very high risk of recurrence. That suggests that maybe there's a population that we need to rethink pursuing surgery in, because they're very likely to recur despite that surgery anyway.

Again, this is a really, really exciting space. I think there's a lot still to learn about it. I can certainly see this guiding management a number of different tumor types to help guide who needs treatment escalation, who we can safely not give chemotherapy to.

There are a number of great trials going on, CIRCULATE-US and COBRA studies come to mind in colorectal cancer, so would highly encourage people to enroll to those. Again, really exciting time and a lot to come.

Source:

Kamath S. “ctDNA in Gastrointestinal Malignancies.” Presented at: Great Debates and Updates in Gastrointestinal Malignancies; March 30-April 1; Chicago, IL