2023 North America Conference on Lung Cancer (NACLC) - Posters and Abstracts-PP01.79 (Poster) ctDNA dynamics, prognostic markers, and RESULTS mechanisms of resistance in tepotinib-treated MET exon 14 skipping (METex14) NSCLC in the VISION trial

PP01.79 (Poster) ctDNA dynamics, prognostic markers, and RESULTS mechanisms of resistance in tepotinib-treated MET exon 14 skipping (METex14) NSCLC in the VISION trial

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This document presents the results of a study on the dynamics, prognostic markers, and mechanisms of resistance in MET exon 14 skipping non-small cell lung cancer (NSCLC) patients treated with tepotinib. The study analyzed the largest on-treatment liquid biopsy biomarker dataset for a MET inhibitor in METex14 skipping NSCLC.<br /><br />The results showed that low baseline hepatocyte growth factor (HGF) and low relative on-treatment change in soluble MET were associated with better outcomes. Patients with baseline undetectable METex14 skipping in liquid biopsy samples (but detectable in tissue biopsy) had more favorable treatment outcomes, likely due to lower tumor burden and lower circulating tumor DNA shedding.<br /><br />The study also found that patients whose circulating tumor DNA remained undetectable for METex14 skipping during treatment and those who achieved confirmed molecular response had improved outcomes. This supports the use of liquid biopsy for monitoring response and resistance.<br /><br />Secondary MET mutations and bypass pathway activation were identified as potential mechanisms of resistance to tepotinib.<br /><br />The study provides valuable insights into the use of liquid biopsy testing and interpretation of results in METex14 skipping NSCLC. It highlights the importance of baseline HGF and soluble MET levels as prognostic markers and the potential of liquid biopsy for predicting treatment response and identifying resistance mechanisms.<br /><br />Overall, these findings contribute to the growing evidence base for liquid biopsy testing and provide important information for the management of METex14 skipping NSCLC patients treated with tepotinib.

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Richard O'Hara

Keywords

dynamics

prognostic markers

mechanisms of resistance

MET exon 14 skipping non-small cell lung cancer

tepotinib

liquid biopsy

hepatocyte growth factor

soluble MET

tumor burden

circulating tumor DNA shedding