2024 Targeted Therapies for Lung Cancer (TTLC) - Abstracts & Posters-PP01.34 Viray

PP01.34 Viray - Abstract

Pdf Summary

This study examines resistance mechanisms in EGFR exon 20 insertion mutation lung cancers treated with various inhibitors. The results show that EGFR-T790M and EGFR-C797S mutations lead to resistance to certain inhibitors like osimertinib and poziotinib, and cross-resistance to others like zipalertib, furmonertinib, and sunvozertinib. The research used preclinical models to study the effects of different mutations on inhibitor efficacy. It was found that while some inhibitors had favorable therapeutic windows for specific mutations, the presence of EGFR-T790M or EGFR-C797S negated this effect. Notably, furmonertinib and sunvozertinib showed the most promising results across different mutation scenarios. The study emphasizes the need for developing new inhibitors that can overcome resistance mutations like EGFR-T790M and EGFR-C797S. Overall, the findings suggest the limitations of current inhibitors and stress the importance of developing next-generation inhibitors with improved efficacy and reduced vulnerability to on-target resistance.

Keywords

EGFR exon 20 insertion mutation

resistance mechanisms

EGFR-T790M mutation

EGFR-C797S mutation

inhibitors

osimertinib

poziotinib

zipalertib

furmonertinib

sunvozertinib