Related Experiment Video

Updated: Apr 15, 2026

Establishing Dual Resistance to EGFR-TKI and MET-TKI in Lung Adenocarcinoma Cells In Vitro with a 2-step Dose-escalation Procedure
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Establishing Dual Resistance to EGFR-TKI and MET-TKI in Lung Adenocarcinoma Cells In Vitro with a 2-step Dose-escalation Procedure

Published on: August 11, 2017

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Treating acquired resistance to EGFR-tyrosine kinase inhibitors:still a work in progress

Nathan A Pennell1

  • 1Assistant Professor, Solid Tumor Oncology, Cleveland Clinic Taussig Cancer Institute, 9500 Euclid Ave., R-35, Cleveland, OH 44195, USA.

Translational Lung Cancer Research
|March 26, 2015
PubMed

Insights

Afatinib, an irreversible EGFR inhibitor, did not improve survival in advanced non-small cell lung cancer (NSCLC) patients who had progressed on prior EGFR TKIs. This suggests irreversible inhibitors may not be viable for overcoming acquired resistance in NSCLC.

Area of Science:

  • Oncology
  • Pharmacology
  • Medical Research

Background:

  • Metastatic non-small cell lung cancer (NSCLC) with EGFR mutations often responds to EGFR TKIs.
  • Acquired resistance to EGFR TKIs is a significant challenge in NSCLC treatment.
  • Irreversible EGFR inhibitors like afatinib are being investigated to overcome this resistance.

Purpose of the Study:

  • To evaluate the efficacy of afatinib in patients with advanced NSCLC who progressed after prior EGFR TKI therapy.
  • To determine if afatinib improves overall survival compared to placebo in this patient population.

Main Methods:

  • The study was a randomized phase 2b/3 trial (LUX-Lung 1).
  • Patients with advanced NSCLC who had progressed after at least 12 weeks of benefit from EGFR TKIs were included.
  • Afatinib was compared against placebo.

Main Results:

  • Afatinib did not demonstrate an improvement in overall survival compared to placebo.
  • The study's broad entry criteria may have included patients without true acquired resistance.

Conclusions:

  • The failure of afatinib to improve survival in this trial raises questions about the viability of irreversible EGFR inhibitors for overcoming acquired resistance in NSCLC.
  • Further research is needed to identify appropriate patient populations for irreversible EGFR inhibitors.
Keywords:
EGFRacquired resistancetyrosine kinase inhibitors

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