Metastatic CRC: Role of ctDNA in Treatment Selection


Insights on the role of circulating tumor DNA in treatment selection for patients with metastatic colorectal cancer.


Cathy Eng, MD, FACP, FASCO: Now that we’re talking about anti-EGFR therapy and given your expertise in circulating tumor DNA, do you want to comment about how you may look at the role of circulating tumor DNA [ctDNA] when you’re considering a patient for anti-EGFR therapy, and what it can mean?

Arvind Dasari, MD, MS: Building on what doctors Michael Foote, MD; Arpana Parikh, MD; and Suneel Kamath, MD said about selecting patients by looking beyond just the primary biomarker. Looking at other mechanisms of resistance. There’s an analysis done of the PARADIGM study [NCT02394795] and it is truly remarkable that out of the 800 patients who were enrolled, they had baseline ctDNA in over 700 of the patients. That’s amazing. What they did in this patient population, they looked at the ctDNA profile to look at mutations in KRAS, NRAS, PIK3CA, BRAF, and amplifications in HER2 [human epidermal growth factor receptor 2] and MET. Also, they looked at rare fusions like NTRK and RET.

These are all thought to be potential resistance mechanisms against EGFR therapy. About 70% or so were hyperselection negative. That is, they did not have any of these mutations. In these patients, the panitumumab arm did significantly better than the bevacizumab arm. Overall, patients who had any of these alterations did worse than the patients who did not have any alterations. In this subgroup, the panitumumab arm did worse than the bevacizumab arm. It is truly compelling data that remains to be validated and likely will be practice-changing once validated.

Cathy Eng, MD, FACP, FASCO: And recently it was presented at ASCO GI [American Society of Clinical Oncology Gastrointestinal Cancer Symposium Annual Meeting], if I’m correct?

Arvind Dasari, MD, MS: Correct. You’re absolutely right.

Cathy Eng, MD, FACP, FASCO: Could you reiterate once again the importance of EGFR therapy and being HER2 positive and the impact on treatment decision-making?

Arvind Dasari, MD, MS: As was already mentioned, there’s a body of data that was built up retrospectively showing that patients who have HER2/neu amplified tumors, even if they are EGFR RAS wild type and even if left-sided may not respond to anti-EGFR therapy. This was prospectively tested in the SWOG1613 trial [NCT03365882]. Those results were also presented at ASCO GI 2023. That trial evaluated trastuzumab plus pertuzumab vs cetuximab plus irinotecan in this patient population in those who had HER2 amplified tumors. What they found was that the amount of amplification correlated with response. Patients who had more HER2-amplified tumors did better with anti-HER2 therapy and did worse with anti-EGFR therapy.

Cathy Eng, MD, FACP, FASCO: Thank you so much.

Transcript edited for clarity.

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