Cited by 174Lung Cancer Treatments and MutationsCancer Genomics and DiagnosticsHER2/EGFR in Cancer Research

The DOI matches its Crossref record; 30 of the 33 references it cites were found in a registry or an index; 1 of the 20 sources its claims cite were checked for support.

Concurrent Genetic Alterations Predict the Progression to Target Therapy in EGFR-Mutated Advanced NSCLC

Open access

Abstract

Introduction: EGFR‐mutant NSCLC displays diverse outcomes to tyrosine kinase inhibitor (TKI) treatment. Because co‐occurring genomic alterations might describe different biological subsets of patients with this cancer, exploring co‐occurring genomic alterations that impact patients’ outcomes using a comprehensive gene panel is potentially important. Methods: This retrospective cohort study was conducted with the panel‐sequencing data acquired from January 2014 to May 2017, and clinical outcome data collected until February 2018. This study includes all eligible patients who possess panel‐sequencing data before treatment with first‐/second‐generation EGFR‐TKIs (cohort 1) or third‐generation EGFR‐TKIs following initial EGFR‐TKI failure (cohort 2). Results: Seventy‐five patients (mean [SD] age, 58.5 [11.0] years; 68.0% women) were included in cohort 1, and 82 patients (mean [SD] age, 57.3 [9.1] years; 67.1% women) were included in cohort 2. In cohort 1, alterations in TP53 were independently associated with worse progression‐free survival (PFS) (hazard ratio [HR]: 2.02; 95% confidence interval [CI]: 1.04–3.93; p = 0.038) in multivariate analysis. In cohort 2, TP53 mutation was associated with significantly worse PFS (8.9 versus 12.8 months; p = 0.029). RB1 mutation was significantly associated with worse (median PFS, 1.9 versus 11.7 months; p < 0.001). PTEN mutation was associated with significantly worse PFS (2.6 versus 10.3 months; p = 0.001). MDM2 amplification was associated with worse PFS (6.6 versus 10.4 months; p = 0.025). In cohort 2, multivariate analysis revealed that alterations in TP53 (HR: 2.23; 95% CI: 1.16–4.29; p = 0.017), RB1 (HR: 5.62; 95% CI: 1.96–16.13; p = 0.001), PTEN (HR: 5.84; 95% CI: 1.56–21.85; p = 0.009), and MDM2 (HR: 2.46; 95% CI: 1.02–5.94; p = 0.046) were independently associated with worse PFS. Conclusions: Co‐occurring genomic alterations detected by panel sequencing are associated with the clinical outcomes of EGFR‐TKI treatment in NSCLC.

Overview

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Registry

Crossref · 10.1016/j.jtho.2018.10.150

Cites

30 of 30 references verified0 citation errors · 0 not checkable

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Claims the paper makes

28 Own result · 14 Not checked yet · 11 Own interpretation · 7 Own method · 1 Partly supported · accuracy not yet measured

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  • Probably not a substantial claim. 18
  • It may state two separate claims as one. 7
21 of 21
  • The paper relies on this without support.

    PTEN suppresses tumors by inhibiting PI3K pathway activation.

    “PTEN acts as a tumor suppressor by inhibiting PI3K pathway activation.”
  • The paper relies on this without support.

    The PI3K pathway lies downstream of EGFR signaling.

    “Given that the PI3K pathway is downstream of the EGFR-signaling pathway”
  • The paper relies on this without support.

    High-throughput sequencing analysis can systematically detect clinically meaningful genetic alterations and identify patients likely to respond to targeted agents.

    “Statistical analysis of high-throughput sequencing data enables systematic detection of clinically meaningful genetic alterations, making it possible to identify patients potentially sensitive to targeted agents.”
  • The paper relies on this without support.

    NGS results from pre-treatment tumor samples represent the genomic state relevant to subsequent EGFR-TKI response.

    “Cohort 1 included patients with NGS results obtained before treatment with first-/second-generation EGFR-TKIs”
  • The paper relies on this without support.

    PFS is a valid measure of clinical benefit from EGFR-TKI treatment.

    “Progression-free survival (PFS) and overall survival (OS) were measured from the first day of treatment with EGFR-TKI to tumor progression and death, respectively.”
5 of 5

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Metadata

Authors
Kim, Y., Lee, B., Shim, J. H., Lee, S.-H., Park, W.-Y., Choi, Y.-L., Sun, J.-M., Ahn, J. S., Ahn, M.-J., & Park, K.
Affiliations
Samsung Medical Center (KR)
Corresponding author
Lee, Se-Hoon
Venue
Journal of Thoracic Oncology
Publisher
Elsevier BV
Published
2019-02
Volume
14
Issue
2
Pages
193-202
ISSN
1556-0864 (ISSN-L)
OpenAlex
W2898978171
Cited by
174
References
33
Citations by year
2026: 12 · 2025: 24 · 2024: 18 · 2023: 29 · 2022: 24 · 2021: 22 · 2020: 32 · 2019: 13
FWCI
12.61
Type
journal article
Language
en
Open access
Locations
  • Journal of Thoracic Oncology (publishedVersion)
  • PubMed (publishedVersion)
Funders
  • Ministry of Trade, Industry and Energy
  • National Research Foundation of Korea
Topics
  • Health Sciences › Medicine › Pulmonary and Respiratory Medicine › Lung Cancer Treatments and Mutations
  • Life Sciences › Biochemistry, Genetics and Molecular Biology › Cancer Research › Cancer Genomics and Diagnostics
  • Health Sciences › Medicine › Oncology › HER2/EGFR in Cancer Research
Keywords
EGFR-mutant non-small cell lung cancer, tyrosine kinase inhibitors, anti-EGFR therapy, TP53 mutation, RB1 mutation, PTEN mutation, MDM2 amplification, progression-free survival, treatment resistance, predictive biomarkers, third-generation EGFR-TKI, comprehensive genomic profiling, molecular subtypes, prognostic factors
MeSH terms
Progression-Free Survival, Aged, Antineoplastic Agents, Carcinoma, Non-Small-Cell Lung, DNA, Neoplasm, Female, Humans, Lung Neoplasms, Male, Middle Aged, Mutation, Retrospective Studies, Signal Transduction, Survival Rate, Tumor Suppressor Protein p53, Sequence Analysis, DNA, Ubiquitin-Protein Ligases, Protein Kinase Inhibitors, PTEN Phosphohydrolase, Proto-Oncogene Proteins c-mdm2, Retinoblastoma Binding Proteins, High-Throughput Nucleotide Sequencing, ErbB Receptors

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