2023 World Conference on Lung Cancer (Posters)-EP12.01. Molecular Characteristics and Response to TKIs in NSCLC Patients with EGFR Exon 19 Insertions

EP12.01. Molecular Characteristics and Response to TKIs in NSCLC Patients with EGFR Exon 19 Insertions - PDF(Abstract)

Pdf Summary

This study aimed to investigate the molecular characteristics and response to EGFR TKIs in non-small cell lung cancer (NSCLC) patients with EGFR exon 19 insertions (19ins). Next-generation sequencing was performed on 100 NSCLC patients with EGFR 19ins, and their molecular profiles were compared to those with common EGFR exon 19 deletions (19del) or 19delins. The overall frequency of EGFR 19ins in lung cancer patients was found to be 0.14%, with the majority of cases carrying the p.I740_K745dup mutation. <br /><br />At baseline, TP53 was the most commonly mutated gene in patients with 19ins, followed by PIK3CA and TERT. Compared to patients with 19del/delins, those with 19ins had a lower frequency of TP53 mutations and a higher frequency of PIK3CA and TERT alterations. Additionally, 19ins patients exhibited lower tumor mutational burden and chromosomal instability compared to 19del/delins at the genomic level. <br /><br />Among patients treated with first-generation TKIs, those with 19ins had worse survival outcomes compared to those with 19del/delins. Subgroup analysis indicated that patients with 19ins tended to benefit less from gefitinib treatment compared to other TKIs. In vitro experiments suggested that the EGFR I740_K745dup mutation might be more sensitive to afatinib. Importantly, no on-target resistance mutations, such as T790M, were identified in patients with 19ins. <br /><br />The comprehensive analysis of EGFR 19ins in NSCLC patients revealed distinct genomic characteristics and clinical response compared to 19del/delins. These findings contribute to a better understanding of these uncommon driver mutations and may help guide clinical decisions and the development of more precise therapeutic options for patients with EGFR 19ins.

Asset Subtitle

Yang Shao

Meta Tag

Speaker Yang Shao

Topic Metastatic NSCLC: Targeted Therapy - EGFR/HER2

Keywords

molecular characteristics

response to EGFR TKIs

non-small cell lung cancer

NSCLC patients

EGFR exon 19 insertions

p.I740_K745dup mutation

TP53 mutations

PIK3CA alterations

TERT alterations

first-generation TKIs