Repeated rebiopsy for detection of EGFR T790M mutation in patients with advanced-stage lung adenocarcinoma: Associated factors and treatment outcomes of Osimertinib

PLoS One. 2024 Sep 19;19(9):e0310079. doi: 10.1371/journal.pone.0310079. eCollection 2024.

Abstract

Objectives: This study was performed to investigate the detection rate of EGFR T790M mutation by repeated rebiopsy, to identify the clinical factors related to repeated rebiopsy, and to assess survival outcomes according to the methods and numbers of repeated rebiopsies in patients with lung adenocarcinoma who received sequential osimertinib after failure of previous 1st or 2nd generation EGFR-tyrosine kinase inhibitors.

Methods: This retrospective study included patients with advanced-stage lung adenocarcinoma who were confirmed to have EGFR T790M mutation and to have received osimertinib from January 2020 to February 2021 at Samsung Medical Center. The presence of T790M mutation was assessed based on either plasma circulating tumor DNA (ctDNA) or tissue specimens. Results A total of 443 patients underwent rebiopsy, with 186 (42.0%) testing positive for the T790M mutation by the sixth rebiopsy. The final analysis included 143 eligible patients. Progression-free survival was not significantly different in terms of the methods (tissue: 13.3 months, 95% confidence interval [CI]: [9.4, 23.5] vs plasma: 11.1 months, 95% CI: [8.1, 19.4], p = 0.33) and numbers (one: 13.4 months, 95% CI: [9.4, 23.5] vs two or more: 11.0 months, 95% CI: [8.1, 14.8], p = 0.51) of repeated rebiopsies. Longer overall survival (OS) was found in patients in whom T790M was detected by tissue specimens rather than by plasma ctDNA (2-year OS rate: 81.7% for tissue vs 63.9% for plasma, p = 0.0038). Factors related to the lower numbers of rebiopsies included age and bone metastasis. Factor associated with T790M detection in tissue rather than in plasma was pleural metastasis, while advanced tumor stage was related to T790M confirmation in plasma rather than in tissue.

Conclusions: Repeated rebiopsy for T790M detection in patients with NSCLC can increase the detection rate of the mutation. Detection of T790M by plasma ctDNA might be related to poor survival outcomes.

MeSH terms

  • Acrylamides* / therapeutic use
  • Adenocarcinoma of Lung* / drug therapy
  • Adenocarcinoma of Lung* / genetics
  • Adenocarcinoma of Lung* / pathology
  • Adult
  • Aged
  • Aged, 80 and over
  • Aniline Compounds* / therapeutic use
  • Antineoplastic Agents / therapeutic use
  • Biopsy
  • Circulating Tumor DNA / blood
  • Circulating Tumor DNA / genetics
  • ErbB Receptors* / genetics
  • Female
  • Humans
  • Indoles
  • Lung Neoplasms* / drug therapy
  • Lung Neoplasms* / genetics
  • Lung Neoplasms* / mortality
  • Lung Neoplasms* / pathology
  • Male
  • Middle Aged
  • Mutation*
  • Neoplasm Staging
  • Progression-Free Survival
  • Protein Kinase Inhibitors / therapeutic use
  • Pyrimidines
  • Retrospective Studies
  • Treatment Outcome

Substances

  • osimertinib
  • Acrylamides
  • ErbB Receptors
  • Aniline Compounds
  • EGFR protein, human
  • Circulating Tumor DNA
  • Protein Kinase Inhibitors
  • Antineoplastic Agents
  • Indoles
  • Pyrimidines

Grants and funding

This work was supported by the National Research Foundation of Korea (NRF) grant funded by the Korea government (MSIT) (2020R1A2C2006282). The funders had no role in study design, data collection and analysis, decision to publish, or preparation of the manuscript.