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Exosomal miRNA Analysis in Non-small Cell Lung Cancer NSCLC Patients' Plasma Through qPCR: A Feasible Liquid Biopsy Tool
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Clinical analysis by next-generation sequencing for NSCLC patients with MET amplification resistant to osimertinib

Yubo Wang1, Li Li1, Rui Han1

  • 1Department of Respiratory Medicine, Daping Hospital, Third Military Medical University, Chongqing, PR China.

Lung Cancer (Amsterdam, Netherlands)
|March 25, 2018
PubMed
Abstract

Insights

MET amplification is a key resistance mechanism to osimertinib in lung adenocarcinoma, leading to worse progression-free survival. Combination therapy with EGFR-TKI and crizotinib shows promise for patients with MET amplification after osimertinib resistance.

Area of Science:

  • Oncology
  • Genetics
  • Pharmacology

Background:

  • Osimertinib resistance is a significant challenge in treating advanced lung adenocarcinoma.
  • MET amplification is an emerging mechanism of resistance to osimertinib.
  • Limited data exists on MET amplification's impact on prognosis and effective treatment strategies post-osimertinib resistance.

Purpose of the Study:

  • To investigate acquired MET amplification as a resistance mechanism to osimertinib in lung adenocarcinoma.
  • To analyze the correlation between MET amplification and clinical prognosis (progression-free survival and overall survival) after osimertinib resistance.
  • To evaluate the efficacy of combination therapy in patients with acquired MET amplification.

Main Methods:

  • Longitudinal plasma and tissue samples from lung adenocarcinoma patients before and after osimertinib treatment were analyzed using capture-based sequencing.
  • Kaplan-Meier analysis was employed to assess the correlation between MET amplification and patient prognosis.
  • Clinical data from a cohort of 13 patients progressing after osimertinib resistance was retrospectively reviewed.

Main Results:

  • Acquired MET amplification was identified as a resistance mechanism in lung adenocarcinoma patients treated with osimertinib.
  • Patients with MET amplification after osimertinib resistance exhibited significantly inferior median progression-free survival (3.5 months vs. 9.9 months) and overall survival (15.6 months vs. 30.7 months).
  • Two patients with acquired MET amplification achieved partial responses with a combination of first-generation EGFR-TKI and crizotinib.

Conclusions:

  • MET amplification is a clinically relevant resistance mechanism to osimertinib in lung adenocarcinoma, associated with poor outcomes.
  • Combination therapy with EGFR-TKI and crizotinib represents a potential therapeutic strategy for patients with acquired MET amplification post-osimertinib resistance.
  • Further research is warranted to validate these findings in larger cohorts and explore optimal treatment combinations.
Keywords:
CrizotinibMET amplificationOsimertinibResistance

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