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

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 patie...

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Main Authors: Zhixin Chen, Jiali Gong, Jing Chen, Lan Yang, Shumin Hu, Lingru Chen, Hongyang Lu
Format: Article
Language:English
Published: Taylor & Francis Group 2025-12-01
Series:Annals of Medicine
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Online Access:https://www.tandfonline.com/doi/10.1080/07853890.2025.2488109
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author Zhixin Chen
Jiali Gong
Jing Chen
Lan Yang
Shumin Hu
Lingru Chen
Hongyang Lu
author_facet Zhixin Chen
Jiali Gong
Jing Chen
Lan Yang
Shumin Hu
Lingru Chen
Hongyang Lu
author_sort Zhixin Chen
collection DOAJ
description 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.
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spelling doaj-art-d79f9482692041c9a18bd3f693a40e072025-08-20T01:53:58ZengTaylor & Francis GroupAnnals of Medicine0785-38901365-20602025-12-0157110.1080/07853890.2025.2488109Clinical outcomes of EGFR-TKI in advanced lung squamous cell carcinoma and EGFR-TKI remodel tumor immune microenvironmentZhixin Chen0Jiali Gong1Jing Chen2Lan Yang3Shumin Hu4Lingru Chen5Hongyang Lu6Zhejiang Key Laboratory of Diagnosis &amp; Treatment Technology on Thoracic Oncology (lung and esophagus), Zhejiang Cancer Hospital, Hangzhou Institute of Medicine (HIM), Chinese Academy of Sciences, Hangzhou, P.R. ChinaDepartment of Hematology and Oncology, Ningbo No. 2 Hospital, Ningbo, P. R. ChinaZhejiang Key Laboratory of Diagnosis &amp; Treatment Technology on Thoracic Oncology (lung and esophagus), Zhejiang Cancer Hospital, Hangzhou Institute of Medicine (HIM), Chinese Academy of Sciences, Hangzhou, P.R. ChinaZhejiang Key Laboratory of Diagnosis &amp; Treatment Technology on Thoracic Oncology (lung and esophagus), Zhejiang Cancer Hospital, Hangzhou Institute of Medicine (HIM), Chinese Academy of Sciences, Hangzhou, P.R. ChinaZhejiang Key Laboratory of Diagnosis &amp; Treatment Technology on Thoracic Oncology (lung and esophagus), Zhejiang Cancer Hospital, Hangzhou Institute of Medicine (HIM), Chinese Academy of Sciences, Hangzhou, P.R. ChinaZhejiang Key Laboratory of Diagnosis &amp; Treatment Technology on Thoracic Oncology (lung and esophagus), Zhejiang Cancer Hospital, Hangzhou Institute of Medicine (HIM), Chinese Academy of Sciences, Hangzhou, P.R. ChinaZhejiang Key Laboratory of Diagnosis &amp; Treatment Technology on Thoracic Oncology (lung and esophagus), Zhejiang Cancer Hospital, Hangzhou Institute of Medicine (HIM), Chinese Academy of Sciences, Hangzhou, P.R. ChinaBackground 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.https://www.tandfonline.com/doi/10.1080/07853890.2025.2488109Lung squamous cell carcinomaEGFR mutationresistance mechanismtumor immune microenvironmenttherapy
spellingShingle Zhixin Chen
Jiali Gong
Jing Chen
Lan Yang
Shumin Hu
Lingru Chen
Hongyang Lu
Clinical outcomes of EGFR-TKI in advanced lung squamous cell carcinoma and EGFR-TKI remodel tumor immune microenvironment
Annals of Medicine
Lung squamous cell carcinoma
EGFR mutation
resistance mechanism
tumor immune microenvironment
therapy
title Clinical outcomes of EGFR-TKI in advanced lung squamous cell carcinoma and EGFR-TKI remodel tumor immune microenvironment
title_full Clinical outcomes of EGFR-TKI in advanced lung squamous cell carcinoma and EGFR-TKI remodel tumor immune microenvironment
title_fullStr Clinical outcomes of EGFR-TKI in advanced lung squamous cell carcinoma and EGFR-TKI remodel tumor immune microenvironment
title_full_unstemmed Clinical outcomes of EGFR-TKI in advanced lung squamous cell carcinoma and EGFR-TKI remodel tumor immune microenvironment
title_short Clinical outcomes of EGFR-TKI in advanced lung squamous cell carcinoma and EGFR-TKI remodel tumor immune microenvironment
title_sort clinical outcomes of egfr tki in advanced lung squamous cell carcinoma and egfr tki remodel tumor immune microenvironment
topic Lung squamous cell carcinoma
EGFR mutation
resistance mechanism
tumor immune microenvironment
therapy
url https://www.tandfonline.com/doi/10.1080/07853890.2025.2488109
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