Related Experiment Video

Updated: Dec 18, 2025

Establishment and Characterization of Three Afatinib-resistant Lung Adenocarcinoma PC-9 Cell Lines Developed with Increasing Doses of Afatinib
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Emerging Treatment Paradigms for EGFR-Mutant Lung Cancers Progressing on Osimertinib: A Review

Andrew J Piper-Vallillo1,2,3, Lecia V Sequist2,3, Zofia Piotrowska2,3

  • 1Department of Medicine, Division of Medical Oncology, Beth Israel Deaconess Medical Center, Boston, MA.

Journal of Clinical Oncology : Official Journal of the American Society of Clinical Oncology
|June 20, 2020
PubMed

Insights

Osimertinib resistance in advanced EGFR-mutant non-small cell lung cancer (NSCLC) is complex, driven by EGFR-dependent and independent mechanisms. Identifying these resistance pathways is crucial for guiding subsequent treatment strategies.

Area of Science:

  • Oncology
  • Molecular Biology
  • Genetics

Background:

  • Osimertinib is a standard first-line treatment for advanced EGFR-mutant non-small cell lung cancer (NSCLC).
  • Understanding resistance mechanisms to osimertinib is critical for managing disease progression and selecting effective second-line therapies.

Purpose of the Study:

  • To review and characterize the heterogeneous mechanisms of osimertinib resistance in advanced EGFR-mutant NSCLC.
  • To provide an evidence-based approach for evaluating and managing patients who progress on first-line osimertinib.

Main Methods:

  • Analysis of data from six osimertinib resistance series.
  • Identification and categorization of EGFR-dependent and independent resistance mechanisms.

Main Results:

  • Common resistance mechanisms include MET alterations (7%-24%), EGFR C797X mutations (0%-29%), small cell lung cancer (SCLC) transformation (2%-15%), and oncogene fusions (1%-10%).
  • Resistance profiles are heterogeneous, involving both EGFR-dependent and independent pathways.

Conclusions:

  • Osimertinib resistance in NSCLC is multifaceted, necessitating comprehensive evaluation.
  • An algorithmic approach and knowledge of clinical trials are essential for optimizing post-progression management.

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