2022 World Conference on Lung Cancer (ePosters)-EP16.03-021. Developing of EGFR resistant mutations to Tyrosine Kinase Inhibitors (TKI) in Non-Small Cell Lung Cancer (NSCLC)

EP16.03-021. Developing of EGFR resistant mutations to Tyrosine Kinase Inhibitors (TKI) in Non-Small Cell Lung Cancer (NSCLC)

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This study focused on the development of resistance mutations to tyrosine kinase inhibitors (TKIs) in non-small cell lung cancer (NSCLC) with an EGFR mutation. The researchers analyzed a large cohort of EGFR mutant NSCLC tumors to determine the prevalence of resistance mutations.<br /><br />The known resistance mechanisms to TKIs in EGFR mutant NSCLC include acquired EGFR mutations, copy number amplifications, gene fusion events, and histological transformation. The study aimed to identify the frequency of these resistance mutations in the cohort.<br /><br />The tumor samples were submitted for NextGen Sequencing and whole exome sequencing to identify resistance mutations. Additionally, other markers such as PD-L1 expression and total somatic mutations were measured.<br /><br />The results showed that among the 27,848 NSCLC tumors analyzed, 3,223 had an EGFR sensitizing mutation. Of these, only 60 (0.2%) had common missense resistance mutations, including C797, L718, G724, and G721. The L718 mutations were found to co-occur with L858R or exon 19 mutations, and some also co-occurred with T790M mutations.<br /><br />In terms of other co-alterations, the study found that 13% of the resistance mutant cohort had a high tumor mutational burden (TMB), 41% had high PD-L1 expression, and 2% had dMMR/MSI-H.<br /><br />The study concluded that acquired resistance in EGFR mutant NSCLC is heterogeneous, and the frequency of resistance mutations is still low. The researchers attribute this to a lack of sequencing of EGFR resistant tumors. They suggest that next-generation sequencing (NGS) should be used to evaluate patients with resistant EGFR mutant lung cancers.<br /><br />Overall, this study provides valuable insights into the prevalence of resistance mutations in EGFR mutant NSCLC and highlights the importance of NGS in understanding and managing resistance to TKIs in this population.

Asset Subtitle

Luis Raez

Meta Tag

Speaker Luis Raez

Topic Tumour Biology and Biomarkers - Molecular Profiling and Targeted Therapies

Keywords

tyrosine kinase inhibitors

non-small cell lung cancer

NSCLC

EGFR mutation

resistance mutations

acquired EGFR mutations

copy number amplifications

gene fusion events

histological transformation

NextGen Sequencing