Genomic characterisation of de novo EGFR copy number gain and its impact on the efficacy of first-line EGFR-tyrosine kinase inhibitors for EGFR mutated non-small cell lung cancer

Background: Non-small cell lung cancer (NSCLC) patients with epidermal growth factor receptor (EGFR) mutation generally respond well to epidermal growth factor receptortyrosine kinase inhibitors (EGFR-TKIs). However, genomic characterisation of de novo EGFR copy number gain (CNG) and its impact on the efficacy of first-line EGFR-TKIs remains unclear.Methods: This multicenter, retrospective and real-world study included two cohorts that enroled EGFR mutant NSCLC patients. EGFR CNG was tested by next-generation sequencing of untreated tissue specimens. Cohort 1 detected the impact of EGFR CNG on firstline EGFR-TKIs treatment, and cohort 2 explored the genomic characterisation.Results: Cohort 1 enroled 355 patients from four cancer centres between January 2013 and March 2022. The patients were divided into three groups, included the EGFR non-CNG, EGFR CNG, and EGFR uncertain-CNG. No significant difference in progression-free survival (PFS) was found between the three groups (10.0 months vs. 10.8 months vs. 9.9 months, respectively, p = 0.384). Furthermore, the overall response rate was not statistically significant in the EGFR CNG group compared to the EGFR non-CNG or uncertain arm (70.3% vs. 63.2% vs. 54.5%, respectively, p = 0.154). Cohort 2 included 7876 NSCLC patients with 16.4% showing EGFR CNG. Gene mutations such as TP53, IKZF1, RAC1, MYC, MET, CDKN2A/B and alterations of the metabolic-related and ERK signalling pathway were Conclusions: De novo EGFR CNG had no effect on the efficacy of first-line EGFR-TKI treatment in EGFR mutant NSCLC patients, and tumours with EGFR CNG had more complex genomic profiles than those without.(c) 2023 Elsevier Ltd. All rights reserved.

Automated summary

This retrospective study explored the impact of EGFR copy number gain (CNG) on the efficacy of first-line EGFR-TKIs in NSCLC patients with EGFR mutation. The results showed that EGFR CNG had no effect on the efficacy of first-line EGFR-TKI treatment in EGFR mutant NSCLC patients.