2022 World Conference on Lung Cancer (ePosters)-EP08.02-120. MET Alterations at Presentation in NSCLC Patients Harboring EGFR Mutations and ALK, RET and ROS1 fusions

EP08.02-120. MET Alterations at Presentation in NSCLC Patients Harboring EGFR Mutations and ALK, RET and ROS1 fusions

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A study was conducted to determine the frequency of MET gene amplification, MET mutations, and MET mRNA high expression in patients with non-small cell lung cancer (NSCLC) who had EGFR mutations and ALK, ROS1, and RET fusions. Biopsies from NSCLC patients were analyzed using next-generation sequencing (NGS) for mutations and copy number variations, as well as nCounter for mRNA analysis. Immunohistochemistry (IHC) and fluorescent in situ hybridization (FISH) were used for confirmatory purposes. <br /><br />Out of 72 EGFR-mut NSCLC patients, 4% (3/72) had MET amplification, while no mutations were observed in the MET kinase domain. Two out of 26 patients with available mRNA data showed very high expression of MET. Among the 53 fusion-positive patients (ALK, ROS1, RET), 2% (1/53) had MET amplification and 4% (2/53) had very high levels of MET mRNA.<br /><br />Paired biopsies from 3 patients with MET amplification at progression to targeted therapies were also analyzed. One patient treated with osimertinib showed positive MET expression by IHC but negative by FISH, while the other two pretreatment biopsies were negative by both techniques.<br /><br />The study suggests that a significant number of NSCLC patients with targetable alterations show MET amplification or very high expression of MET at baseline, while mutations are rare. The results highlight the potential benefit of combination treatments in these patients. Further clinical trials are needed to explore the efficacy of first-line combination therapy in this setting.<br /><br />The findings of this study contribute to the understanding of MET alterations in NSCLC patients and provide insights for future treatment strategies.

Asset Subtitle

Núria Jordana

Meta Tag

Speaker Núria Jordana

Topic Metastatic Non-small Cell Lung Cancer - Molecular Targeted Treatments

Keywords

MET gene amplification

MET mutations

MET mRNA high expression

non-small cell lung cancer

EGFR mutations

ALK fusions

ROS1 fusions

RET fusions

next-generation sequencing

copy number variations