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Treating EGFR mutation resistance in non-small cell lung cancer - role of osimertinib

Valentina Mazza1, Federico Cappuzzo1,2

  • 1Department of Oncology-Hematology.

The Application of Clinical Genetics
|August 11, 2017
PubMed

Insights

EGFR mutations drive non-small cell lung cancer (NSCLC) treatment. While EGFR-TKIs are effective, resistance develops, often via T790M mutations, necessitating new therapeutic strategies.

Area of Science:

  • Oncology
  • Molecular Biology
  • Pharmacology

Background:

  • Epidermal Growth Factor Receptor (EGFR) mutations define a subset of non-small cell lung cancer (NSCLC) with distinct clinical features.
  • First- and second-generation EGFR-tyrosine kinase inhibitors (EGFR-TKIs) are first-line treatments for EGFR-mutant NSCLC, but acquired resistance is inevitable.

Purpose of the Study:

  • To review the role of EGFR mutations in NSCLC treatment.
  • To discuss the mechanism of acquired resistance to EGFR-TKIs, particularly the T790M mutation.
  • To highlight the efficacy and approval of osimertinib in overcoming T790M-mediated resistance.

Main Methods:

  • Review of Phase II and Phase III clinical trial data for osimertinib.
  • Analysis of mechanisms of acquired resistance to EGFR-TKIs.
  • Discussion of current treatment paradigms for EGFR-mutant NSCLC.

Main Results:

  • Osimertinib, a third-generation EGFR-TKI, effectively targets the T790M resistance mutation.
  • Clinical studies demonstrate the efficacy and tolerability of osimertinib in advanced EGFR-mutant NSCLC post-progression on prior EGFR-TKIs.
  • Osimertinib has gained regulatory approval for this indication.

Conclusions:

  • Osimertinib represents a significant advancement in treating EGFR-mutant NSCLC resistant to earlier TKIs.
  • Acquired resistance to osimertinib is emerging, creating an unmet need for novel treatment strategies.
  • Future directions include combination therapies and the development of next-generation compounds.
Keywords:
EGFR-mutant non-small-cell Lung cancerT790M mutationacquired resistanceosimertinibthird generation EGFR-TKI

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