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(Slides)

Back to course

Pdf Summary

A case report titled "NGS Reveals Convergent Acquired Resistance and Newly Emerging Driver Involving MET Alterations in NSCLC" discusses the occurrence of two important MET alterations in non-small cell lung cancer (NSCLC) - MET exon 14 skipping (METex14skipping) and amplification (METamp). These two alterations have distinct roles in the development of NSCLC. The report highlights that while METex14skipping is a key driver mutation that is mutually exclusive with EGFR activating alterations, METamp represents one of the common mechanisms of acquired resistance to EGFR-TKIs.<br /><br />The report presents a case of a 60-year-old Thai woman diagnosed with stage IV lung adenocarcinoma in 2019. The patient initially had a partial response to Osimertinib, but later developed signs and symptoms of disease progression. A repeat tissue-based genomic profiling was performed using a 50-gene hotspot next-generation sequencing (NGS) panel called APEX. The profiling revealed the presence of EGFR exon 19 deletion and the newly acquired high-level METamp as potential mechanisms of resistance to Osimertinib.<br /><br />Further analysis showed the emergence of METex14skipping, indicating the evolution of a new clone harboring a distinct driver alteration from the primary EGFR-mutated tumor. This case emphasizes the importance of repeat tissue testing using a broad NGS panel to identify actionable biomarkers for guiding treatment selection and management after progression on first-line EGFR-TKI.<br /><br />Based on the genomic profiling results, the patient was treated with Capmatinib as a second-line therapy, leading to a reduction in the size of the liver lesion and an ongoing partial response as of the last follow-up.<br /><br />This case report highlights the unique occurrence of both METex14skipping and METamp in the same NSCLC patient, demonstrating the role of the MET pathway in oncogenic addiction and the effectiveness of targeted therapy with capmatinib. The findings emphasize the need for comprehensive genomic profiling to identify potentially actionable biomarkers and inform treatment decisions in NSCLC patients.

Asset Subtitle

Chek Kun Tan

Meta Tag

Speaker Chek Kun Tan

Topic Metastatic NSCLC: Targeted Therapy - EGFR/HER2

Keywords

NGS

MET alterations

NSCLC

MET exon 14 skipping

METamp

EGFR-TKIs

tissue-based genomic profiling

Osimertinib resistance

Capmatinib

comprehensive genomic profiling