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ASCO 2022 | Acquired resistance to anti-EGFR therapy in colorectal cancer

Christine Megerdichian Parseghian, MD, The University of Texas MD Anderson Cancer Center, Houston, TX, discusses overcoming acquired resistance to anti-EGFR therapies. A study was conducted on acquired resistance mutations occurring within the first- or third-line setting via the investigation of plasma samples from three large Phase III trials. Patients being treated in the third-line setting had significantly higher rates of acquired resistance mutations than those treated in the first-line. Additionally, patients who were being treated with chemotherapy plus anti-EGFR had significantly lower rates of acquired mutations compared to patients treated with anti-EGFR monotherapy. These findings raise implications on how best to overcome both acquired genomic and transcriptomic resistance to anti-EGFR therapies. This interview took place at the American Society of Clinical Oncology (ASCO) 2022 Annual Meeting in Chicago, IL.

Transcript (edited for clarity)

Obviously a big area of my interest is how to overcome resistance to anti EGFR therapy, whether it be through re challenge efforts or combination regimens. So we were the first to really look at acquired resistance mutations occurring with the first line or with later line like third line therapy. So we looked at plasma samples from three large phase III trials, both in the first line and third line setting, and actually found that after in the third line setting, patients had a significantly higher rate of acquired resistance mutations and this varied by line of therapy and type of therapy...

Obviously a big area of my interest is how to overcome resistance to anti EGFR therapy, whether it be through re challenge efforts or combination regimens. So we were the first to really look at acquired resistance mutations occurring with the first line or with later line like third line therapy. So we looked at plasma samples from three large phase III trials, both in the first line and third line setting, and actually found that after in the third line setting, patients had a significantly higher rate of acquired resistance mutations and this varied by line of therapy and type of therapy.

So patients also, we looked at patients who had gotten chemotherapy with anti EGFR versus anti EGFR alone, and also found that those getting chemotherapy with anti EGFR had lower rates of acquired mutations, somewhat of a crossover resistance that we were kind of seeing. So this has significant implications in terms of how to overcome resistance to anti EGFR therapy and raises questions about not only acquired genomic mutations that could kind of be contributing to this resistance, but also non genomic mechanisms, transcriptomic mechanisms of resistance that really need to be addressed in the future when it comes to thinking about how to best re challenge these patients.

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