Abstract
Background
Data from studies looking at both EGFR and ERBB2 exon 20 insertion mutations (-20ins) in the same cohort of patients with non-small cell lung cancer (NSCLC) are limited.
Objective
The purpose of this study was to analyze EGFR/ERBB2-20ins in all-stage NSCLC patients to reveal their histological and molecular features, and to retrospectively evaluate the results of first-line real-world systemic treatments in patients with advanced-stage disease.
Patients and Methods
We collected 13,920 formalin-fixed paraffin-embedded NSCLC specimens. Clinicopathological features were recorded and DNA-based next-generation sequencing was performed. First-line systemic treatment data were obtained via chart review.
Results
In total, 414 (2.97%) EGFR-20ins cases and 666 (4.78%) ERBB2-20ins cases were identified. Both were more common in women, non-smokers, and patients with adenocarcinoma. The incidence of EGFR/ERBB2-20ins in adenocarcinoma is inversely proportional to the degree of invasion; 77 and 26 variants were detected in EGFR-20ins and ERBB2-20ins cases, respectively. The most common concurrently mutated genes were TP53 and RB1. In invasive adenocarcinoma, lepidic components were more common in EGFR/ERBB2-20ins-alone cases than in those with other concurrent mutated genes. In EGFR-/ERBB2-20ins patients, there was no significant difference in progression-free survival (PFS) or treatment response to first-line systemic treatments in this study. There was no significant difference in PFS or treatment response among patients with different EGFR/ERBB2-20ins variants and those with or without concurrent mutated genes.
Conclusions
EGFR/ERBB2-20ins is more common in early lung adenocarcinoma. EGFR-20ins had more variants. In both cohorts, the results for first-line systemic treatments showed no significant difference.
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Acknowledgements
The authors thank Di Peng, Xiao Zou, Xi Li, Jing Wang, and Wenqi Gao (Burning Rock Biotech) for their assistance with the data analysis.
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This work was supported by the Interdisciplinary Program of Shanghai Jiao Tong University (project number ZH2018QNA66) and the National Natural Science Foundation of China (No. 82003154 to CX; No. 82372669 to YH).
Conflict of interest
Ruiying Zhao, Jiaqi Li, Lianying Guo, Chan Xiang, Shengnan Chen, Jikai Zhao, Jinchen Shao, Lei Zhu, Min Ye, Gang Qin, Tianqing Chu, and, Yuchen Han declare they have no conflicts of interest that might be relevant to the contents of this manuscript.
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All procedures performed in this study involving human participants were in accordance with the ethical standards of the institutional and national research committees and with the 1964 Helsinki Declaration and its later amendments or comparable ethical standards. The study was reviewed and approved by the Ethics Committee of Shanghai Chest Hospital.
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Informed consent was obtained from all individual participants included in this study.
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The datasets generated and/or analyzed during the current study are available from the corresponding author upon reasonable request.
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Author contributions
RZ: Conceptualization, methodology, funding acquisition, writing—original draft. JL: Methodology, investigation, writing—original draft. LG: Data curation, methodology. CX, SC, JZ, JS, LZ, MY, GQ: Methodology. TC: Supervision, writing – review and editing. YH: Supervision, writing—review and editing, funding acquisition.
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Zhao, R., Li, J., Guo, L. et al. EGFR and ERBB2 Exon 20 Insertion Mutations in Chinese Non-small Cell Lung Cancer Patients: Pathological and Molecular Characterization, and First-Line Systemic Treatment Evaluation. Targ Oncol 19, 277–288 (2024). https://doi.org/10.1007/s11523-024-01042-3
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DOI: https://doi.org/10.1007/s11523-024-01042-3