Abstract 5378
Background
The purpose of this study was to analyze the frequency and type of genetic alterations in tyrosine kinase inhibitor (TKI)-naïve vs. TKI-treated NSCLC patients. We report a spectrum of resistance mechanisms upon TKI treatment in liquid biopsies using a comprehensive hybrid capture NGS test (HC-NGS).
Methods
We retrospectively collected mutational data of 200 solid NSCLC biopsies of treatment-naïve patients that were routinely tested for clinically relevant mutations by HC-NGS at our institution. In addition, we analyzed mutational data from 367 liquid biopsies of NSCLC patients whose disease progressed under treatment. Solid tumor biopsies and liquid biopsies were tested using a 39-gene HC-NGS panel including 39 clinically relevant genes (NEOselect, LOD 3.0%; NEOliquid, LOD 0.1%; NEO New Oncology GmbH, Cologne).
Results
Primary HC-NGS diagnostics in TKI -aïve patients revealed 12% (24/200) TKI-sensitive EGFR mutations, 5.0% (10/200) Alk/ROS/RET translocations, 0.5% (1/200) BRAF V600E, and in one patient a MET Exon 14 skipping mutation (0.5%, 1/200). Further, a variety of clinically relevant mutations were detected, among others, prognostically relevant TP53 mutations at a frequency of 52.0% (104/200). In addition, we tested 367 liquid biopsies from relapse patients. 30.9% (113/367) pts had an activating EGFR mutation and therefore presumably received EGFR TKI treatment. Of the 113 pts, 39.8% (45/113) developed a T790M resistance mutation and 1.8% (2/113) an additional MET amplification.
Conclusions
HC-NGS allows for comprehensive analysis of somatic tumor aberrations in the primary diagnostic setting as well as in the relapse scenario. Mechanisms of primary oncogenic activation as well as mechanisms of resistance are heterogeneous and include point mutations, translocations and gene amplifications. Therefore, HC-NGS should be used for diagnosis in both, the primary and the relapse setting.
Clinical trial identification
Legal entity responsible for the study
Hematopathology Hamburg.
Funding
Has not received any funding.
Editorial Acknowledgement
Disclosure
L.C. Heukamp: Affiliations: Hematopathology Hamburg, NEO New Oncology. M. Tiemann: Anstellungsverhaltnis oder Führungsposition: CEO Institut für Heamatopathologie Hamburg Beratungs- bzw. Gutachtertätigkeit; Advisory boards: Novartis, Boehringer, Roche, AstraZeneca; Honorare erhalten von: Vortragshonorare: Novartis, Boehringer, Roche, AstraZeneca. All other authors have declared no conflicts of interest.
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