Differential Responses to Targeted Therapies in Non-Small Cell Lung Cancer: A Comparative Analysis of Outcomes in Patients with Single EGFR Mutation and Concurrent Gene Alterations

Linh Tu Le,1,2 Nhung Viet Nguyen,3 Huy Le Trinh,4,5 Quang Van Le,4– 6 Trang Huyen Thi Dao,7,8 Son Nguyen Ngoc,7 Luong Dinh Van,1,2 Trang Thi Nguyen7– 10 1Department of Oncology, National Lung Hospital, Hanoi, 100000, Vietnam; 2Department of Tuberculosis and Lung Disease, Hanoi Medical University, Ha...

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Main Authors: Le LT, Nguyen NV, Trinh HL, Van Le Q, Dao THT, Nguyen Ngoc S, Van LD, Thi Nguyen T
Format: Article
Language:English
Published: Dove Medical Press 2025-07-01
Series:The Application of Clinical Genetics
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Online Access:https://www.dovepress.com/differential-responses-to-targeted-therapies-in-non-small-cell-lung-ca-peer-reviewed-fulltext-article-TACG
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Summary:Linh Tu Le,1,2 Nhung Viet Nguyen,3 Huy Le Trinh,4,5 Quang Van Le,4– 6 Trang Huyen Thi Dao,7,8 Son Nguyen Ngoc,7 Luong Dinh Van,1,2 Trang Thi Nguyen7– 10 1Department of Oncology, National Lung Hospital, Hanoi, 100000, Vietnam; 2Department of Tuberculosis and Lung Disease, Hanoi Medical University, Hanoi, 100000, Vietnam; 3Department of Pulmonology, University of Medicine and Pharmacy, Vietnam National University, Hanoi, 100000, Vietnam; 4Department of Oncology, Hanoi Medical University, Hanoi, 100000, Vietnam; 5Department of Oncology and Palliative Care, Hanoi Medical University Hospital, Hanoi Medical University, Hanoi, 100000, Vietnam; 6Vietnam National Cancer Hospital, Hanoi, 100000, Vietnam; 7Hanoi Medical University Hospital, Hanoi, 100000, Vietnam; 8Department of Biology and Medical Genetic, Hanoi Medical University, Hanoi, 100000, Vietnam; 9Genetic Counseling Center, Hanoi Medical University Hospital, Hanoi, 100000, Vietnam; 10Hanoi Medical University – Thanh Hoa Campus, Thanh Hoa, 440000, VietnamCorrespondence: Trang Thi Nguyen, Genetic Counseling Center, Hanoi Medical University Hospital, Hanoi, 100000, Vietnam, Email trangnguyen@hmu.edu.vnBackground: Epidermal growth factor receptor tyrosine kinase inhibitors (EGFR-TKIs) improve the quality of life in individuals with EGFR mutation-positive non-small cell lung cancer (NSCLC). This study evaluates the treatment outcomes of EGFR-mutant NSCLC patients with concurrent gene alterations, aiming to determine their predictive significance concerning responses to EGFR-TKI therapy.Materials and Methods: We conducted a retrospective cohort study using next-generation sequencing (NGS) data from January 2019 to June 2023. Patients were categorized into two groups: those with a single EGFR mutation (Group 1) and those with concurrent EGFR mutations (Group 2).Results: Among 109 patients with EGFR mutations, 72 showed partial responses (66.1%), one had a complete response (0.9%), and 17 had stable disease (15.6%); 19 experienced progressive disease (17.4%). The overall response rate (ORR) was 67%, and the disease control rate (DCR) was 82.6%. Progression-free survival (PFS) was 15.03 months (95% CI: 13.17– 16.89) in the single EGFR mutation group and 11.00 months (95% CI: 9.95– 12.05) in the concurrent mutations group (P = 0.001). Among 43 patients with concurrent mutations, those with ALK mutations had the longest PFS (13.43 months), followed by PIK3CA (11.00 months), while MET alterations showed the shortest PFS (4.77 months).Conclusion: Concurrent gene alterations in EGFR-mutant NSCLC are associated with reduced efficacy of EGFR-TKIs. Patients with KRAS, BRAF, ROS1, or MET mutations have poorer predictive outcomes compared to those without these alterations.Keywords: EGFR, NSCLC, concurrent mutations, targeted therapy, treatment outcomes
ISSN:1178-704X