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Treatment patterns and clinical outcomes in Chinese patients with NSCLC with MET alterations resistant to EGFR‑TKI therapy

  • Authors:
    • Cailu Shen
    • Siying Zhang
    • Xiaoli Wang
    • Di Shen
    • Xiaosong Ge
    • Yong Mao
  • View Affiliations / Copyright

    Affiliations: Department of Cancer Diagnosis and Treatment Center, Affiliated Hospital of Jiangnan University, Wuxi, Jiangsu 214000, P.R. China, Wuxi Medical College of Jiangnan University, Wuxi, Jiangsu 214000, P.R. China, Department of Pathology, Affiliated Hospital of Jiangnan University, Wuxi, Jiangsu 214000, P.R. China
    Copyright: © Shen et al. This is an open access article distributed under the terms of Creative Commons Attribution License.
  • Article Number: 81
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    Published online on: July 4, 2025
       https://doi.org/10.3892/mco.2025.2876
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Abstract

The present study evaluated therapeutic strategies and clinical outcomes in Chinese patients with mesenchymal‑epithelial transition (MET) alterations in non‑small cell lung cancer (NSCLC) who were progressing on epidermal growth factor receptor‑tyrosine kinase inhibitor (EGFR‑TKI), aiming to address the unmet need of overcoming MET‑driven resistance. A real‑world study was conducted, involving eligible patients with NSCLC treated at Jiangnan University Affiliated Hospital between February 2022 and April 2024. Based on the treatment regimen, patients were categorized into three groups: MET‑TKI combined with EGFR‑TKI, chemotherapy‑based regimen, and other regimens. The primary outcomes were the objective response rate (ORR), time to treatment failure (TTF), post‑progression survival (PPS) and adverse events (AEs). A total of 32 patients were included in the analysis. The MET‑TKI plus EGFR‑TKI group (n=10) achieved the highest ORR at 55.6%, followed by the chemotherapy‑based regimen group (n=15) at 42.9% and the other regimens group (n=7) at 14.3%. The median TTF was 9.5 months for the MET‑TKI plus EGFR‑TKI group, compared with 4.4 and 3.6 months for the chemotherapy‑based and other regimens groups, respectively (P=0.748). Similarly, the median PPS was 14.4 months in the MET‑TKI plus EGFR‑TKI group, compared with 9.4 and 7.0 months in the chemotherapy‑based and other regimens groups, respectively (P=0.733). Treatment‑related AEs varied among the groups, with nausea, peripheral edema and rash being the most common in the MET‑TKI plus EGFR‑TKI group. In conclusion, the combination of MET‑TKI and EGFR‑TKI demonstrates promising benefits in terms of TTF, PPS and ORR, underscoring its potential as a viable treatment option. The modest improvements observed, coupled with the inherent limitations of the present study, emphasize the necessity for further research to optimize treatment strategies and gain a deeper understanding of the long‑term efficacy of combination therapy in addressing MET‑driven resistance to EGFR‑TKI.
View Figures

Figure 1

Representative IHC and FISH images of
MET. (A) Strong membranous expression by IHC (3+ score),
magnification 20x and (B) gene amplification by FISH (MET/CEP7 ≥2).
CEP7, centromere of chromosome 7; FISH, fluorescence in situ
hybridization; IHC, immunohistochemistry; MET,
mesenchymal-epithelial transition.

Figure 2

Flow chart of patient enrollment in
the present study. NSCLC, non-small cell lung cancer; EGFR,
epidermal growth factor receptor; MET, mesenchymal-epithelial
transition; TKI, tyrosine kinase inhibitor.

Figure 3

Treatment effectiveness in individual
patients. (A) A waterfall plot showing the best responses for each
of the 30 evaluable patients. (B) A swimmer plot of 10 patients
receiving MET-TKI plus EGFR-TKI and (C) a plot for one of seven
patients treated with other regimens followed by EGFR-TKI
resistance, with a time to failure survival of 3.6 months. EGFR,
epidermal growth factor receptor; MET, mesenchymal-epithelial
transition; TKI, tyrosine kinase inhibitor.

Figure 4

Survival analysis for the study
population. Kaplan-Meier curves for (A) time to treatment failure
survival in all patients, (B) time to treatment failure survival
stratified by treatment regimens, (C) post-progression survival in
all patients and (D) post-progression survival stratified by
treatment regimens. EGFR, epidermal growth factor receptor; MET,
mesenchymal-epithelial transition; TKI, tyrosine kinase
inhibitor.

Figure 5

Representative radiographic images of
two patients who were treated with MET-TKI in combination with
EGFR-TKI after developing resistance to EGFR-TKI. EGFR, epidermal
growth factor receptor; MET, mesenchymal-epithelial transition;
TKI, tyrosine kinase inhibitor.
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Spandidos Publications style
Shen C, Zhang S, Wang X, Shen D, Ge X and Mao Y: Treatment patterns and clinical outcomes in Chinese patients with NSCLC with <em>MET</em> alterations resistant to EGFR‑TKI therapy. Mol Clin Oncol 23: 81, 2025.
APA
Shen, C., Zhang, S., Wang, X., Shen, D., Ge, X., & Mao, Y. (2025). Treatment patterns and clinical outcomes in Chinese patients with NSCLC with <em>MET</em> alterations resistant to EGFR‑TKI therapy. Molecular and Clinical Oncology, 23, 81. https://doi.org/10.3892/mco.2025.2876
MLA
Shen, C., Zhang, S., Wang, X., Shen, D., Ge, X., Mao, Y."Treatment patterns and clinical outcomes in Chinese patients with NSCLC with <em>MET</em> alterations resistant to EGFR‑TKI therapy". Molecular and Clinical Oncology 23.3 (2025): 81.
Chicago
Shen, C., Zhang, S., Wang, X., Shen, D., Ge, X., Mao, Y."Treatment patterns and clinical outcomes in Chinese patients with NSCLC with <em>MET</em> alterations resistant to EGFR‑TKI therapy". Molecular and Clinical Oncology 23, no. 3 (2025): 81. https://doi.org/10.3892/mco.2025.2876
Copy and paste a formatted citation
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Spandidos Publications style
Shen C, Zhang S, Wang X, Shen D, Ge X and Mao Y: Treatment patterns and clinical outcomes in Chinese patients with NSCLC with <em>MET</em> alterations resistant to EGFR‑TKI therapy. Mol Clin Oncol 23: 81, 2025.
APA
Shen, C., Zhang, S., Wang, X., Shen, D., Ge, X., & Mao, Y. (2025). Treatment patterns and clinical outcomes in Chinese patients with NSCLC with <em>MET</em> alterations resistant to EGFR‑TKI therapy. Molecular and Clinical Oncology, 23, 81. https://doi.org/10.3892/mco.2025.2876
MLA
Shen, C., Zhang, S., Wang, X., Shen, D., Ge, X., Mao, Y."Treatment patterns and clinical outcomes in Chinese patients with NSCLC with <em>MET</em> alterations resistant to EGFR‑TKI therapy". Molecular and Clinical Oncology 23.3 (2025): 81.
Chicago
Shen, C., Zhang, S., Wang, X., Shen, D., Ge, X., Mao, Y."Treatment patterns and clinical outcomes in Chinese patients with NSCLC with <em>MET</em> alterations resistant to EGFR‑TKI therapy". Molecular and Clinical Oncology 23, no. 3 (2025): 81. https://doi.org/10.3892/mco.2025.2876
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