Somatic Copy-Number Alterations in Plasma Circulating Tumor DNA from Advanced EGFR-Mutated Lung Adenocarcinoma Patients

Anna Buder, Ellen Heitzer, Julie Waldispühl-Geigl, Sabrina Weber, Tina Moser, Maximilian J Hochmair, Klaus Hackner, Peter Errhalt, Ulrike Setinek, Martin Filipits

Research output: Journal article (peer-reviewed)Journal article

8 Citations (Scopus)

Abstract

BACKGROUND: To assess the clinical relevance of genome-wide somatic copy-number alterations (SCNAs) in plasma circulating tumor DNA (ctDNA) from advanced epidermal growth factor receptor (EGFR)-mutated lung adenocarcinoma patients.

METHODS: We included 43 patients with advanced EGFR T790M-positive lung adenocarcinoma who were treated with osimertinib after progression under previous EGFR-TKI therapy. We performed genomic profiling of ctDNA in plasma samples from each patient obtained pre-osimertinib and after patients developed resistance to osimertinib. SCNAs were detected by shallow whole-genome plasma sequencing and EGFR mutations were assessed by droplet digital PCR.

RESULTS: SCNAs in resistance-related genes (rrSCNAs) were detected in 10 out of 31 (32%) evaluable patients before start of osimertinib. The presence of rrSCNAs in plasma before the initiation of osimertinib therapy was associated with a lower response rate to osimertinib (50% versus 81%, p = 0.08) and was an independent predictor for shorter progression-free survival (adjusted HR 3.33, 95% CI 1.37-8.10, p = 0.008) and overall survival (adjusted HR 2.54, 95% CI 1.09-5.92, p = 0.03).

CONCLUSIONS: Genomic profiling of plasma ctDNA is clinically relevant and affects the efficacy and clinical outcome of osimertinib. Our approach enables the comprehensive assessment of SCNAs in plasma samples of lung adenocarcinoma patients and may help to guide genotype-specific therapeutic strategies in the future.

Original languageEnglish
Article number618
JournalBiomolecules
Volume11
Issue number5
DOIs
Publication statusPublished - May 2021

Keywords

  • Acrylamides/therapeutic use
  • Adenocarcinoma/pathology
  • Adenocarcinoma of Lung/genetics
  • Aged
  • Aged, 80 and over
  • Aniline Compounds/therapeutic use
  • Biomarkers, Pharmacological/blood
  • Carcinoma, Non-Small-Cell Lung/pathology
  • Cell-Free Nucleic Acids/blood
  • Circulating Tumor DNA/genetics
  • DNA Copy Number Variations/genetics
  • Drug Resistance, Neoplasm/genetics
  • ErbB Receptors/genetics
  • Female
  • Humans
  • Liquid Biopsy/methods
  • Lung/pathology
  • Lung Neoplasms/genetics
  • Male
  • Middle Aged
  • Progression-Free Survival
  • Protein Kinase Inhibitors/therapeutic use

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