Colorectal Cancer: Insights on ctDNA and Retesting for HER2 Expression

A panel of experts discuss the role of ctDNA and their practices for retesting HER2 expression to guide treatment for colorectal cancer.


Michael Foote, MD: There’s such an interesting world we’re entering into with circulating tumor DNA [ctDNA] to monitor not only what mutations are occurring in the initial phase but also the persistence of subclones. We saw with studies like the TOMAS trial (NCT02398058) in Italy from the Alberto Bardelli lab at the Candiolo Cancer Institute that patients that initially had EGFR therapy developed resistance, and then they were checked again for RAS mutations. They didn’t have RAS mutations; they were able to be re-treated. Could we see some sequencing where we’re using circulating tumor DNA to evaluate the continued persistence of certain resistance subclones or the absence, and could we re-treat people with therapy? And how does that work with EGFR inhibitors? It’s a very exciting, maybe confusing, world that we’re going towards.

Cathy Eng, MD, FACP, FASCO: You brought up a very good point. I meant to discuss it earlier. We were at a lecture today and we did discuss it for a large part of the day. But should we be retesting patients for HER2 expression?

Aparna Parikh, MD: So this is controversial. I retest before T-DXd [trastuzumab deruxtecan].

Cathy Eng, MD, FACP, FASCO: I do too.

Aparna Parikh, MD: And I’m not sure how much change there is with HER2 in colon cancer at least. But I think, again, given the toxicity profile, if there’s a safe place to biopsy that’s been my practice to re-biopsy.

Michael Foote, MD: I’ll say. I had a patient who was HER2+ on a lymph node that we took out about a year and a half ago. And we retested a surgical sample for her lung nodule, and her HER2 was negative. So it was just a different subclone, but it was really important to us because I would’ve put her on therapy. And so, we ended up putting her just on normal chemotherapy. It’s just an anecdote.

Cathy Eng, MD, FACP, FASCO: It’s still an important point. Another thought?

Arvind Dasari, MD, MS: I completely agree. I think, especially at the risk of toxicities, certainly retesting makes a lot of sense. I’m curious, what are your thoughts about tissue biopsy vs ctDNA and this retesting?

Aparna Parikh, MD: I’ll do both still and I think that the blood with HER2, even tissue testing isn’t quite harmonized yet. And so, is it 6? Is it 8? Is it 20? And then you had 1.7.

Cathy Eng, MD, FACP, FASCO: I know.

Michael Foote, MD: I know, right? You just threw a wrench in everything.

Aparna Parikh, MD: Yes, in everything. And I think with the blood, with amplifications, I’m really looking forward to seeing, I think the MOUNTAINEER trial (NCT03043313), which eventually they’ll present all the ctDNA data because they did do ctDNA on those patients. And it’ll be really interesting to see. But I think currently it’s a little bit tough because particularly for amplifications it’s a little bit all over the place still.

Arvind Dasari, MD, MS: Indeed. Absolutely.

Cathy Eng, MD, FACP, FASCO: Well, thank you so much.

Transcript edited for clarity.

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