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(Slides)

Pdf Summary

This study aimed to understand the molecular characteristics and response to EGFR TKIs in lung cancer patients with EGFR exon 19 insertions (19ins), a rare subtype of exon 19 alterations. Next-generation sequencing was conducted on 100 NSCLCs with EGFR 19ins, and their molecular profiles were compared with common EGFR 19del or 19delins. TP53, PIK3CA, and TERT were the most commonly mutated genes in patients with 19ins, with a lower frequency of TP53 and a higher frequency of PIK3CA and TERT alterations compared to 19del/delins. It was also observed that 19ins had lower levels of tumor mutational burden and chromosomal instability. The overall frequency of EGFR 19ins in lung cancer patients was 0.14%, with two main subtypes identified: p.I740_K745dup (88%) and p.K745_E746insVPVAIK (12%). Patients with 19ins exhibited worse survival outcomes when treated with first-generation TKIs compared to those with 19del/delins. In particular, patients with 19ins benefited the least from gefitinib treatment. T790M was the most common on-target resistance mutation in 19del/delins, but few patients with 19ins exhibited this mutation, and no clear resistance mechanisms were identified. In vitro experiments suggested that the EGFR I740_K745dup mutation might be more sensitive to afatinib. Overall, this study provides valuable insights into the genomic characteristics and clinical response of lung cancer patients with EGFR 19ins, which can inform clinical decisions and the development of targeted therapies for these rare driver mutations.

Asset Subtitle

Yang Shao

Meta Tag

Speaker Yang Shao

Topic Metastatic NSCLC: Targeted Therapy - EGFR/HER2

Keywords

molecular characteristics

response to EGFR TKIs

lung cancer patients

EGFR exon 19 insertions

rare subtype

next-generation sequencing

mutated genes

tumor mutational burden

survival outcomes

targeted therapies