2024 World Conference on Lung Cancer (WCLC) - ePosters-EP.12A.39 MET Point Mutations as the Mechanism of Resistance to EGFR-TKI Therapy: A Case Report of MET H1094Y-Mediated Resistance to Osimertinib Overcome by Capmatinib and a Systematic Review.

EP.12A.39 MET Point Mutations as the Mechanism of Resistance to EGFR-TKI Therapy: A Case Report of MET H1094Y-Mediated Resistance to Osimertinib Overcome by Capmatinib and a Systematic Review.

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The document outlines a case study of a 69-year-old male with metastatic non-small cell lung cancer (NSCLC) harboring an EGFR exon 19 deletion, a common mutation targeted by EGFR tyrosine kinase inhibitors (TKIs). Initially, the patient achieved a partial response with osimertinib monotherapy, but eventually experienced disease progression due to the development of resistance mechanisms, including a new MET H1094Y mutation, which is a rare mutation causing resistance to EGFR-TKI therapy.<br /><br />Upon disease progression, the patient underwent multiple lines of treatment, including targeted therapy with osimertinib and an unsuccessful attempt with immune checkpoint inhibitors. The resistance was confirmed by molecular profiling, which identified the MET H1094Y point mutation alongside an increased allele frequency of the EGFR mutation.<br /><br />The introduction of combination therapy with osimertinib and capmatinib targeted both EGFR and MET pathways and successfully overcame resistance. This resulted in a significant clinical improvement, with a notable reduction in pleural effusions, removal of the indwelling pleural fluid catheter, and cessation of supplemental oxygen use. Repeat blood-based next-generation sequencing showed the disappearance of both the EGFR exon 19 deletion and the MET H1094Y mutation.<br /><br />This case highlights the necessity of molecular profiling at disease progression to identify resistance mutations and guide effective treatment strategies. The results suggest that the MET H1094Y mutation, although rare, can be actionable and effectively managed with combination therapy targeting EGFR and MET. The study emphasizes the need for further research to catalogue additional actionable MET alterations beyond amplification. Overall, the patient's tolerance to the new combination treatment was satisfactory, despite some manageable side effects.

Asset Subtitle

Vanya Aggarwal

Meta Tag

Speaker Vanya Aggarwal

Topic Metastatic Non-small Cell Lung Cancer – Targeted Therapy

Keywords

metastatic non-small cell lung cancer

EGFR exon 19 deletion

EGFR tyrosine kinase inhibitors

osimertinib

MET H1094Y mutation

molecular profiling

combination therapy

capmatinib

resistance mechanisms

next-generation sequencing