NGS-Based ctDNA Profiling After the Resistance of Second-Line Osimertinib for Patient with EGFR-Mutated Pulmonary

Dan Li1, DaFu Yang1, SaiQiong Cui1

  • 1The Second Department of Thoracic Medical Oncology, The Second Hospital of Dalian Medical University, Dalian, Liaoning, People's Republic of China.

Insights

Osimertinib effectively treats EGFR T790M positive non-small-cell lung cancer. However, acquired resistance mechanisms in lung adenocarcinoma patients treated with osimertinib can be detected using circulating tumor DNA (ctDNA) genotyping.

Area of Science:

  • Oncology
  • Molecular Biology
  • Genetics

Background:

  • Osimertinib is a third-generation EGFR tyrosine kinase inhibitor (TKI) used for EGFR T790M positive non-small-cell lung cancer (NSCLC).
  • Acquired resistance to osimertinib is a significant clinical challenge, with heterogeneous underlying mechanisms.
  • Understanding these resistance mechanisms is crucial for improving patient outcomes.

Observation:

  • A case of lung adenocarcinoma with an EGFR L858R mutation is presented.
  • The patient received second-line osimertinib therapy.
  • Multiple osimertinib resistance mechanisms were identified through non-invasive circulating tumor DNA (ctDNA) genotyping.

Findings:

  • Longitudinal ctDNA genotyping revealed acquired resistance mechanisms during osimertinib treatment.
  • Tumor heterogeneity was observed in the development of osimertinib resistance.
  • The study highlights the dynamic nature of resistance in EGFR-mutated NSCLC.

Implications:

  • This case illustrates potential mechanisms of osimertinib resistance during disease progression.
  • Longitudinal monitoring of ctDNA can detect novel acquired resistance and tumor heterogeneity.
  • Non-invasive ctDNA genotyping offers a valuable tool for guiding treatment strategies in NSCLC.