Clinical outcomes of EGFR-TKI in advanced lung squamous cell carcinoma and EGFR-TKI remodel tumor immune microenvironment

Abstract

Background Clinical data is scarce in epidermal growth factor receptor (EGFR)-mutated lung squamous cell carcinoma (LUSC), and the resistance mechanisms to EGFR-tyrosine kinase inhibitor (TKI) is rarely studied. This study aimed to assess the efficacy of EGFR-TKI treatment in EGFR-mutated LUSC patients .Methods Data of a cohort of 99 LUSC patients who were treated with EGFR-TKI and were followed up to October 31, 2023.Results The objective response rate (ORR) of EGFR-mutated LUSC patients was higher than that of EGFR wild-type patients (44.4% vs 4.4%, p < 0.001). The progression-free survival (PFS) of EGFR-mutated LUSC patients receiving EGFR-TKI treatment was significantly longer than that of EGFR wild-type patients (6.4 months vs. 1.3 months; p < 0.001). Resistance mechanisms to EGFR-TKI in EGFR-mutated LUSC patients included secondary T790M mutations, 19 deletion-insertion mutations, MET amplification, histological transformation, and loss of EGFR mutations. The tumor immune microenvironment (TIME) of EGFR-mutated LUSC showed a downregulation of CD4 (p = 0.047) and CD8 (p = 0.14), and an upregulation of PD-L1 (p = 0.0021) after EGFR-TKI treatment failure.Conclusions EGFR-mutated LUSC patients receiving EGFR-TKIs treatment had higher ORR and longer PFS than EGFR wild-type LUSC patients.

Keywords

• Lung squamous cell carcinoma
• EGFR mutation
• resistance mechanism
• tumor immune microenvironment
• therapy