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Plasma Predictive Features in Treating EGFR-Mutated Non-Small Cell Lung Cancer.

Authors
  • Steendam, Christi M J1, 2
  • Veerman, G D Marijn3
  • Pruis, Melinda A1, 3
  • Atmodimedjo, Peggy4
  • Paats, Marthe S1
  • van der Leest, Cor2
  • von der Thüsen, Jan H4
  • Yick, David C Y5
  • Oomen-de Hoop, Esther3
  • Koolen, Stijn L W3
  • Dinjens, Winand N M4
  • van Schaik, Ron H N6
  • Mathijssen, Ron H J3
  • Aerts, Joachim G J V1
  • Dubbink, Hendrikus Jan4
  • Dingemans, Anne-Marie C1, 7
  • 1 Department of Pulmonology, Erasmus MC Cancer Institute, University Medical Center, 3015 GD Rotterdam, The Netherlands. , (Netherlands)
  • 2 Department of Pulmonology, Amphia Hospital, 4818 CK Breda, The Netherlands. , (Netherlands)
  • 3 Department of Medical Oncology, Erasmus MC Cancer Institute, University Medical Center, 3015 GD Rotterdam, The Netherlands. , (Netherlands)
  • 4 Department of Pathology, Erasmus MC Cancer Institute, University Medical Center, 3015 GD Rotterdam, The Netherlands. , (Netherlands)
  • 5 Department of Pathology, Amphia Hospital, 4818 CK Breda, The Netherlands. , (Netherlands)
  • 6 Department of Clinical Chemistry, Erasmus MC Cancer Institute, University Medical Center, 3015 GD Rotterdam, The Netherlands. , (Netherlands)
  • 7 Department of Pulmonology, Maastricht UMC+, 6229 HX Maastricht, The Netherlands. , (Netherlands)
Type
Published Article
Journal
Cancers
Publisher
MDPI AG
Publication Date
Oct 29, 2020
Volume
12
Issue
11
Identifiers
DOI: 10.3390/cancers12113179
PMID: 33138052
Source
Medline
Keywords
Language
English
License
Unknown

Abstract

Although epidermal growth factor receptor (EGFR)-tyrosine kinase inhibitors (TKIs) are the preferred treatment for patients with EGFR-mutated non-small cell lung cancer (NSCLC), not all patients benefit. We therefore explored the impact of the presence of mutations found in cell-free DNA (cfDNA) and TKI plasma concentrations during treatment on progression-free survival (PFS). In the prospective START-TKI study blood samples from 41 patients with EGFR-mutated NSCLC treated with EGFR-TKIs were available. Next generation sequencing (NGS) on cfDNA was performed, and plasma TKI concentrations were measured. Patients without complete plasma conversion of EGFR mutation at week 6 had a significantly shorter PFS (5.5 vs. 17.0 months, p = 0.002) and OS (14.0 vs. 25.5 months, p = 0.003) compared to patients with plasma conversion. In thirteen (second line) osimertinib-treated patients with a (plasma or tissue) concomitant TP53 mutation at baseline, PFS was significantly shorter compared to six wild-type cases; 8.8 vs. 18.8 months, p = 0.017. Erlotinib Cmean decrease of ≥10% in the second tertile of treatment was also associated with a significantly shorter PFS; 8.9 vs. 23.6 months, p = 0.037. We obtained evidence that absence of plasma loss of the primary EGFR mutation, isolated plasma p.T790M loss after six weeks, baseline concomitant TP53 mutations, and erlotinib Cmean decrease during treatment are probably related to worse outcome.

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