2023 World Conference on Lung Cancer (Posters)-EP12.01. NGS Reveals Convergent Acquired Resistance and Newly Emerging Driver Involving MET Alterations in NSCLC: A Case Report

EP12.01. NGS Reveals Convergent Acquired Resistance and Newly Emerging Driver Involving MET Alterations in NSCLC: A Case Report - PDF(Abstract)

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This presentation discusses a case report on a patient with metastatic non-small cell lung cancer (NSCLC) who had acquired resistance to first-line treatment with Osimertinib. The patient, a 60-year-old Thai woman, was initially diagnosed with stage 4 lung adenocarcinoma with brain metastasis and had a partial response to Osimertinib for 22 months. However, she then developed abdominal pain and a progressive primary lung tumor.<br /><br />Molecular profiling using next-generation sequencing (NGS) was performed on a liver biopsy taken from the patient. The analysis revealed the presence of METex14skipping and METamp alterations, which are associated with the MET pathway. METex14skipping is a key driver mutation that is mutually exclusive with EGFR activating mutations/indels, while METamp is one of the common mechanisms of acquired resistance to EGFR-TKIs.<br /><br />This case is unique because it shows the simultaneous detection of both METex14skipping and METamp in the same patient. The presence of these alterations led to the administration of the MET inhibitor, Capmatinib, as second-line treatment. The patient achieved a partial remission and has continued to respond to the treatment.<br /><br />The case highlights the importance of repeat molecular profiling of metastatic tumors using a comprehensive NGS panel. This allows for the identification of potential actionable biomarkers that can guide treatment selection after disease progression on first-line EGFR-TKI therapy.<br /><br />In summary, this case report demonstrates the importance of understanding the oncogenic addiction to the MET pathway in metastatic NSCLC. The detection of METex14skipping and METamp alterations in the patient's tumors guided the choice of targeted therapy, resulting in a positive response. Repeat molecular profiling using NGS can provide valuable information for treatment decisions in patients with acquired resistance to EGFR-TKIs.

Asset Subtitle

Chek Kun Tan

Meta Tag

Speaker Chek Kun Tan

Topic Metastatic NSCLC: Targeted Therapy - EGFR/HER2

Keywords

metastatic non-small cell lung cancer

acquired resistance

Osimertinib

case report

next-generation sequencing

METex14skipping

METamp alterations

MET pathway

EGFR-TKIs

actionable biomarkers