Cell-Free Plasma DNA-Guided Treatment With Osimertinib in Patients With Advanced EGFR-Mutated NSCLC

Anna Buder, Maximilian J Hochmair, Sophia Schwab, Tatjana Bundalo, Peter Schenk, Peter Errhalt, Romana E Mikes, Gudrun Absenger, Kurt Patocka, Bernhard Baumgartner, Ulrike Setinek, Otto C Burghuber, Helmut Prosch, Robert Pirker, Martin Filipits

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

42 Citations (Scopus)

Abstract

INTRODUCTION: Osimertinib is standard treatment for patients with advanced EGFR T790M-mutated non-small-cell lung cancer who have been pre-treated with EGFR-tyrosine kinase inhibitors (TKIs). We studied whether cell-free plasma DNA for T790M detection can be used to select patients for osimertinib treatment in the clinical routine.

METHODS: From April 2015 to November 2016, we included 119 patients with advanced EGFR-mutated non-small-cell lung cancer who had progressed under treatment with an EGFR-TKI. The T790M mutation status was assessed in cell-free plasma DNA by droplet digital polymerase chain reaction in all patients and by tissue analyses in selected patients.

RESULTS: T790M mutations were detected in 85 (93%) patients by analyses of cell-free plasma DNA and in 6 (7%) plasma-negative patients by tumor re-biopsy. Eighty-nine of 91 T790M-positive patients received osimertinib. Median progression-free survival (PFS) was 10.1 months (95% confidence interval [CI]: 8.1-12.1). Median survival was not reached and the 1-year survival was 64%. The response rate was 70% in T790M-positive patients (n = 91) in the intention-to-treat population. PFS trended to be shorter in patients with high T790M copy number (≥10 copies/mL) compared to those with low T790M copy number (<10 copies/mL) (hazard ratio for PFS = 1.72, 95% CI: 0.92-3.2, p = 0.09). A comparable trend was observed for overall survival (hazard ratio for overall survival = 2.16, 95% CI: 0.89-5.25, p = 0.09). No difference in response rate was observed based on T790M copy numbers.

CONCLUSION: Plasma genotyping using digital polymerase chain reaction is clinically useful for the selection of patients who had progressed during first-line EGFR-TKI therapy for treatment with osimertinib.

Original languageEnglish
Pages (from-to)821-830
Number of pages10
JournalJournal of Thoracic Oncology
Volume13
Issue number6
DOIs
Publication statusPublished - Jun 2018

Keywords

  • Acrylamides/pharmacology
  • Adult
  • Aged
  • Aged, 80 and over
  • Aniline Compounds/pharmacology
  • Carcinoma, Non-Small-Cell Lung/drug therapy
  • Female
  • Humans
  • Liquid Biopsy/methods
  • Lung Neoplasms/drug therapy
  • Male
  • Middle Aged
  • Mutation
  • EGFR mutations
  • Advanced non-small cell lung cancer
  • osimertinib
  • liquid biopsy

ASJC Scopus subject areas

  • Oncology
  • Pulmonary and Respiratory Medicine

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