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Emergence of EGFR G724S mutation in EGFR-mutant lung adenocarcinoma post progression on osimertinib

A Oztan1, S Fischer2, A B Schrock1

  • 1Foundation Medicine, Inc., 150 Second Street, Cambridge, MA 02141, USA.

Lung Cancer (Amsterdam, Netherlands)
|August 26, 2017
PubMed

Insights

Acquired resistance to osimertinib, a lung cancer drug, can be identified using genomic profiling. Detecting the EGFR G724S mutation in tissue and blood reveals novel resistance mechanisms in non-small cell lung cancer.

Area of Science:

  • Oncology
  • Molecular Biology
  • Genetics

Background:

  • Epidermal growth factor receptor (EGFR) mutations drive a subset of lung cancers.
  • Osimertinib, a third-generation tyrosine kinase inhibitor (TKI), treats T790M-positive non-small cell lung cancer (NSCLC).
  • Acquired resistance to osimertinib is a clinical challenge with incompletely defined mechanisms.

Observation:

  • The EGFR G724S mutation was identified in two patients with EGFR-driven lung adenocarcinoma who progressed on osimertinib.
  • Detection utilized hybrid-capture based comprehensive genomic profiling (CGP) and circulating tumor DNA (ctDNA) assays.
  • This mutation represents a novel mechanism of osimertinib resistance.

Findings:

  • Hybrid-capture based genomic profiling, analyzing both tissue and ctDNA, successfully identified the EGFR G724S resistance mutation.
  • This highlights the utility of advanced genomic techniques in pinpointing resistance mechanisms.
  • The study provides clinical evidence for a specific EGFR mutation conferring osimertinib resistance.

Implications:

  • Genomic profiling of both tumor tissue and blood is crucial for understanding acquired resistance to targeted therapies like osimertinib.
  • Identifying novel resistance mechanisms can inform future treatment strategies for NSCLC patients.
  • This approach aids in the clinical management of patients progressing on EGFR TKIs.
Keywords:
Acquired resistanceEGFRG724SLung cancerOsimertinibT790M

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