2024 World Conference on Lung Cancer (WCLC) - Posters-P1.12A.02 Efficacy of EGFR-Tyrosine Kinase Inhibitors in Patients with NSCLC Harboring EGFR Exon 19 Insertions: A Report from the LC-SCRUM-Asia

P1.12A.02 Efficacy of EGFR-Tyrosine Kinase Inhibitors in Patients with NSCLC Harboring EGFR Exon 19 Insertions: A Report from the LC-SCRUM-Asia

Back to course

Pdf Summary

This document reports findings on the efficacy of EGFR-tyrosine kinase inhibitors (EGFR-TKIs) in treating non-small cell lung cancer (NSCLC) patients with rare exon 19 insertions in the EGFR gene. This research was conducted by the LC-SCRUM-Asia consortium, a multi-institutional genomic screening project.<br /><br />EGFR exon 19 insertions are uncommon mutations found in approximately 0.1% to 0.4% of NSCLC patients. These mutations are less studied compared to more common EGFR mutations like exon 21 L858R or exon 19 deletions. The study highlights that exon 19 insertions often coexist with TP53 mutations, but not with other driver mutations, suggesting a unique molecular profile.<br /><br />A comprehensive analysis involving clinical, genomic, and preclinical studies was conducted. The study utilized data from the Oncomine Comprehensive Assay, Oncomine Precision Assay, and Oncomine Mutation Load Assay to evaluate clinical-genomic characteristics of these mutations. They also developed Ba/F3 models to test the sensitivity of various generations of TKIs on exon 19 insertion mutations.<br /><br />The results indicate that second-generation EGFR-TKIs show enhanced efficacy against exon 19 insertions compared to other EGFR-TKIs. Structural analyses using AlphaFold and OpenFold confirmed these findings by modeling the interaction of TKIs with the altered EGFR structure.<br /><br />The study underscores the importance of precision medicine in treating NSCLC and provides critical insights into managing exon 19 insertions using second-generation EGFR-TKIs. This could potentially lead to improved clinical outcomes for patients harboring these rare mutations. The research is supported by extensive collaboration among 271 institutions and 22 pharmaceutical companies.

Asset Subtitle

Yuji Uehara

Meta Tag

Speaker Yuji Uehara

Topic Metastatic NSCLC – Targeted Therapy

Keywords

EGFR-tyrosine kinase inhibitors

non-small cell lung cancer

exon 19 insertions

EGFR gene

LC-SCRUM-Asia consortium

TP53 mutations

Oncomine assays

Ba/F3 models

second-generation TKIs

precision medicine