Real-World Analysis of the Efficacy of Rebiopsy and EGFR Mutation Test of Tissue and Plasma Samples in Drug-Resistant Non-Small Cell Lung Cancer

Yonsei Med J. 2019 Jun;60(6):525-534. doi: 10.3349/ymj.2019.60.6.525.

Abstract

Purpose: Standard treatment for cases of non-small cell lung cancer (NSCLC) exhibiting acquired drug resistance includes tumor rebiopsy, epidermal growth factor receptor (EGFR) mutation testing (e.g., for T790M mutations), and the subsequent administration of third-generation EGFR-tyrosine kinase inhibitors (EGFR-TKIs). However, rebiopsies are typically invasive, costly, and occasionally not feasible. Therefore, the present study aimed to assess rebiopsy procedures by analyzing real-world data collected by the ASTRIS study of patients with resistant NSCLC.

Materials and methods: The present study used statistical models to evaluate data collected by the ASTRIS trial (NCT02474355) conducted at Yonsei Cancer Center, including the rebiopsy success rate, incidence of T790M mutations in collected tissue and plasma samples, and association of administered osimertinib treatment efficacy.

Results: In a total of 188 screened patients, 112 underwent rebiopsy. An adequate tumor specimen was obtained in 95 of these patients, the greatest majority of whom (43.8%) were subjected to bronchoscopy. T790M mutations were detected in 53.3% of successfully EGFR-tested rebiopsy samples. A total of 88 patients received osimertinib treatment, and the objective response rate and median progression-free survival time was 44.3% and 32.7 weeks, respectively, among the treated patients overall, but 57.8% and 45.0 weeks, and 35.2% and 20.4 weeks among patients who exhibited T790M-positive tissue (n=45) and plasma (n=54) samples, respectively.

Conclusion: Approximately 60% of patients in the analyzed real-world cohort were eligible for tissue rebiopsy upon NSCLC progression. Osimertinib activity was higher in patients in whom T790M mutations were detected in tissues rather than in plasma samples.

Keywords: EGFR T790M; Non-small cell lung cancer; liquid biopsy; osimertinib; rebiopsy.

MeSH terms

  • Acrylamides
  • Adult
  • Aged
  • Aged, 80 and over
  • Aniline Compounds
  • Antineoplastic Agents / pharmacology
  • Antineoplastic Agents / therapeutic use
  • Biopsy
  • Carcinoma, Non-Small-Cell Lung / blood*
  • Carcinoma, Non-Small-Cell Lung / drug therapy
  • Carcinoma, Non-Small-Cell Lung / genetics*
  • Carcinoma, Non-Small-Cell Lung / pathology
  • Drug Resistance, Neoplasm* / drug effects
  • ErbB Receptors / genetics
  • Feasibility Studies
  • Female
  • Humans
  • Lung Neoplasms / blood*
  • Lung Neoplasms / drug therapy
  • Lung Neoplasms / genetics*
  • Lung Neoplasms / pathology
  • Male
  • Middle Aged
  • Mutation / genetics*
  • Piperazines / pharmacology
  • Piperazines / therapeutic use
  • Progression-Free Survival
  • Protein Kinase Inhibitors / pharmacology
  • Protein Kinase Inhibitors / therapeutic use
  • Treatment Outcome

Substances

  • Acrylamides
  • Aniline Compounds
  • Antineoplastic Agents
  • Piperazines
  • Protein Kinase Inhibitors
  • osimertinib
  • EGFR protein, human
  • ErbB Receptors