Role of ctDNA in therapy selection


Cathy Eng, MD, FACP, FASCO: Now, since we’re talking about anti-EGFR therapy, could you comment on how you think about the role of circulating tumor DNA given your expertise on circulating tumor DNA? [ctDNA] What does it mean if a patient is considered for anti-EGFR therapy?

Dr. Arvind Dasari, M.S.: Built with the input of Dr. Michael Foot, M.D. Alpana Parikh, MD, and Sunil Kamas, MD, discussed selecting patients beyond the primary biomarkers alone. Let’s look at other resistance mechanisms. An analysis of the PRADIGM study was conducted [NCT02394795] And it’s really noteworthy that out of the 800 patients enrolled, more than 700 had baseline ctDNA. It’s amazing. What they did with this patient population was look at the ctDNA profile and look for mutations in the patients. class, NRAS, PIK3CA, BRAFHER2 amplification [human epidermal growth factor receptor 2] and Met. They also noted unusual fusions such as: NTRK and RET.

All of these are believed to be potential resistance mechanisms to EGFR therapy. About 70% were overselected negative. That is, none of these mutations were present. These patients performed significantly better in the panitumumab group than in the bevacizumab group. Overall, patients with any of these changes performed worse than those without. Panitumumab performed worse than bevacizumab in this subgroup. This is truly compelling data that has yet to be validated and could change practice if validated.

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

Dr. Arvind Dasari, M.S.: correct. That’s exactly right.

Cathy Eng, MD, FACP, FASCO: Could you reiterate the importance of EGFR therapy and being HER2 positive, and the implications for treatment decision making?

Dr. Arvind Dasari, M.S.: As already mentioned, patients with HER2/neu-amplified tumors, even EGFR, have a retrospectively constructed data set. RAS It is wild-type and may not respond to anti-EGFR therapy, even on the left side.This was tested prospectively in his SWOG1613 trial [NCT03365882]. These results were also presented at ASCO GI 2023. The trial evaluated trastuzumab plus pertuzumab versus cetuximab plus irinotecan in a population of patients with HER2-amplified tumors. They found that the amount of amplification correlated with response. Patients with more HER2-amplified tumors did better on anti-HER2 therapy and worse on anti-EGFR therapy.

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

I edited the transcript for clarity.

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