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Clinical and molecular characteristics of epidermal growth factor receptor exon 20 insertion mutations in non-small-cell lung cancer

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Abstract

Objective

To evaluate the genomic and immune characteristics of non-small-cell lung cancer (NSCLC) patients with epidermal growth factor receptor (EGFR) exon 20 insertion (ex20ins) mutations from a retrospective dataset with molecular spectrum, tumor mutational burden (TMB), and programmed death-ligand 1 (PD-L1) expression, as well as to evaluate the efficacy of immune checkpoint inhibitors (ICIs).

Methods

A total of 283 patients with EGFR ex20ins mutations who were diagnosed with NSCLC at our hospital from August 2013 to September 2020 were enrolled in this single-center retrospective study.

Results

Among the 283 patients with EGFR ex20ins mutations, 182 patients received next-generation sequencing (NGS) test, and 51 different subtypes of insertion variants were recorded. The most common mutations were A767_V769dup (21.4%), S768_D770dup (19.2%) and A763_Y764insFQEA (7.1%). The most common co-occurring mutations were EGFR amplification (37.9%), TP53 mutation (35.0%) and PIK3CA mutation (8.7%). PD-L1 status was available for 141 patients, and 75.9% (107/141) of these samples showed negative PD-L1 expression. In the 36 cases with TMB tested by NGS, the median TMB was 4.6 mutations/Mb. Then 12 patients received ICIs monotherapy or combination therapy. No severe adverse events were observed.

Conclusion

Low PD-L1 expression and TMB were observed in NSCLC patients harboring EGFR ex20ins mutations. Further investigations are needed to confirm the therapeutic sensitivity of ICIs in this subgroup of EGFR mutations.

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Data availability

All data generated or analysed during this study are included in this published article.

Code availability

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Authors and Affiliations

  1. Department of Medical Oncology, The First Affiliated Hospital of Zhengzhou University, No.1 Eastern Jianshe Road, Zhengzhou, 450052, Henan Province, China

    D. Geng, Q. Guo, S. Huang, H. Zhang, S. Guo & X. Li

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  1. D. Geng
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  2. Q. Guo
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  3. S. Huang
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  4. H. Zhang
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Contributions

DG and XL designed the study and prepared the first draft of the paper. XL is guarantor. QG and SH contributed to the acquisition of the data. HZ and SG were responsible for statistical analysis of the data. QG and SH were responsible for interpretation of data. All authors revised the paper critically for intellectual content and approved the final version. All authors agree to be accountable for the work and to ensure that any questions relating to the accuracy and integrity of the paper are investigated and properly resolved.

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Correspondence to X. Li.

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The study received the support of the Ethics Committee of the First Affiliated Hospital of Zhengzhou University.

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Geng, D., Guo, Q., Huang, S. et al. Clinical and molecular characteristics of epidermal growth factor receptor exon 20 insertion mutations in non-small-cell lung cancer. Clin Transl Oncol 24, 379–387 (2022). https://doi.org/10.1007/s12094-021-02701-x

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