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Detection of Targetable Alterations in Non-small Cell Lung Cancer using Next-generation Sequencing
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Detection of Targetable Alterations in Non-small Cell Lung Cancer using Next-generation Sequencing

Published on: October 10, 2025

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Treatment of EGFR T790M-Positive Non-Small Cell Lung Cancer

Joan Rou-En Choo1, Chee-Seng Tan1, Ross A Soo2,3,4

  • 1Department of Haematology-Oncology, National University Cancer Institute of Singapore, National University Health System, 1E Kent Ridge Road, NUHS Tower Block, Level 7, Singapore, 119228, Singapore.

Targeted Oncology
|February 10, 2018
PubMed

Insights

Osimertinib improves progression-free survival in first-line EGFR-mutated lung cancer. However, resistance develops, often due to triple-mutated EGFR (T790M/C797S), necessitating new treatment strategies.

Area of Science:

  • Oncology
  • Pharmacology
  • Genetics

Background:

  • Tyrosine kinase inhibitors (TKIs) targeting EGFR mutations revolutionized lung cancer treatment.
  • Acquired T790M mutation is a primary resistance mechanism to first-generation EGFR TKIs.
  • Third-generation EGFR TKIs, like osimertinib, target T790M resistance.

Purpose of the Study:

  • To evaluate the efficacy of osimertinib in the first-line treatment of EGFR-mutated lung cancer.
  • To assess osimertinib's effectiveness in patients with brain metastases.
  • To identify emerging resistance mechanisms to osimertinib.

Main Methods:

  • Clinical trial data analysis (FLAURA study).
  • Comparison of osimertinib versus standard first-generation EGFR TKIs.
  • Monitoring of resistance mutations, including T790M and C797S.

Main Results:

  • Osimertinib demonstrated improved progression-free survival (PFS) compared to standard of care.
  • Osimertinib showed promising efficacy in patients with brain metastases.
  • Triple-mutated EGFR (sensitizing mutations/T790M/C797S) is a common resistance mechanism to osimertinib.

Conclusions:

  • Osimertinib is an effective first-line treatment for EGFR-mutated lung cancer, improving PFS.
  • Osimertinib offers a valuable option for patients with brain metastases.
  • Development of novel strategies is crucial to overcome osimertinib resistance, particularly triple mutations.

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