2022 World Conference on Lung Cancer (ePosters)-EP16.03-032. Structure-Based Classification of Chinese Patients with Non-Canonical EGFR-Mutant Non-Small Cell Lung Cancer

EP16.03-032. Structure-Based Classification of Chinese Patients with Non-Canonical EGFR-Mutant Non-Small Cell Lung Cancer

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The document discusses the classification of non-canonical EGFR mutations in Chinese patients with non-small cell lung cancer (NSCLC). The study classifies these mutations into four subtypes: Classical-like, P-loop and αC-helical compressing (PACC), T790M-like, and exon 20 loop insertions. The distribution of these subtypes in cohort 1 was as follows: 60.5% classical-like, 3.77% PACC, 6.86% T790M-like, 1.60% exon 20 insertions, and 27.28% unclassified. The unclassified group primarily consisted of non-classical EGFR 19Del variants. The dominant mutation subtypes varied among the four subgroups. The Classical-like subgroup had L861Q (45.39%) and L858R compound mutation (42.76%), while the PACC subgroup had G719X/S768I compound mutation (28.25%) and the T790M-like subgroup had 19delT790M/C797S compound mutation (50%) and L858R/T790M/C797S (26.09%). The Ex20ins subgroup had D770_N771insSVD (30.67%) and A767_V769dup (25.33%). In cohort 2, the distribution was 60.78% classical-like, 22.55% T790M-like, 10.78% PACC, and 4.9% Ex20ins. Patients in the Classical and T790M-like subgroups had longer time to treatment failure (TTF) compared to the PACC and Ex20ins subgroups. Additionally, the use of the second-generation TKI afatinib significantly improved TTF compared to the first-generation TKI. This study is the first to apply a structure-based classification approach to characterize the mutational landscape of EGFR-mutant NSCLC patients in China. The findings suggest that adopting this approach in clinical practice could improve precision medicine for these patients and assist with future drug development and clinical trial design.

Asset Subtitle

Shun Lu

Meta Tag

Speaker Shun Lu

Topic Tumour Biology and Biomarkers - Molecular Profiling and Targeted Therapies

Keywords

non-canonical EGFR mutations

Chinese patients

non-small cell lung cancer

NSCLC

classification

subtypes

cohort 1

cohort 2

compound mutations

structure-based classification