Monitoring EGFR-T790M mutation in serum/plasma for prediction of response to third-generation EGFR inhibitors in patients with lung cancer

Teresa Morán, Eudald Felip, Joaquim Bosch-Barrera, Itziar de Aguirre, Jose Luis Ramirez, Carles Mesia, Enric Carcereny, Diana Roa, Elia Sais, Yolanda García, Remei Blanco, Silvia Sanchez, Claudia Rosa Villacorta, Cristina Queralt, Jose María Velarde, Rafael Rosell

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2 Citations (Scopus)

Abstract

© Morán et al. Background: Osimertinib is efficacious in lung cancer patients with epidermal growth factor receptor (EGFR) mutations and acquired resistance (AR) to EGFR tyrosine kinase inhibitors due to EGFR-T790M mutation (T790M). We sought to describe T790M changes in serum/plasma during osimertinib therapy and correlate these changes with treatment outcomes. Material and methods: Serum/plasma from EGFR-mutant lung cancer patients with T790M-AR was collected before and during osimertinib treatment. Changes in T790M were evaluated using a peptide-nucleic acid-PCR assay, and correlated with clinical and radiographic response. Results: Thirteen patients were included. Median time on osimertinib treatment was 10.6 months with a median progression-free survival of 13.6 months. Best response to osimertinib was partial response (PR), stable disease (SD) or progression (PD) in 46.1%, 30.8% and 23.1% of patients, respectively. Most of the patients were paucisymptomatic at baseline. Symptom improvement was reported in 66.6% of responder patients; while symptoms remained stable in 75% of patients with SD, and 66% of patients with PD had clinical deterioration. Three patterns of T790M changes during osimertinib treatment were identified. T790 remained detectable with PD or a short-lasting SD in 15.4% of the patients. T790M disappeared in 69.2% of patients with PR or SD. T790M disappeared, despite clinical and/or radiographic progression in 15.4% of the patients. Conclusion: Changes of T790M in serum/plasma in EGFR-mutant lung cancer patients with T790M-AR might be a useful marker of symptomatic and radiographic outcome to osimertinib. Longer follow-up is needed to establish if subsequent emergence of T790M could be a marker of resistance.
Original languageEnglish
Pages (from-to)27074-27086
JournalOncotarget
Volume9
Issue number43
DOIs
Publication statusPublished - 1 Jun 2018

Keywords

  • Acquired resistance
  • EGFR tyrosine kinase inhibitors
  • EGFR-T790M mutation
  • Osimertinib
  • Serum/plasma

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