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Targeting rare and non-canonical driver variants in NSCLC: an uncharted clinical field

Objectives - Implementation of tyrosine kinase inhibitors (TKI) and other targeted therapies was a main advance in thoracic oncology with survival gains ranging from several months to years for non-small-cell lung cancer (NSCLC) patients. High-throughput comprehensive molecular profiling is of key i...

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Hauptverfasser: Volckmar, Anna-Lena (VerfasserIn) , Christopoulos, Petros (VerfasserIn) , Kirchner, Martina (VerfasserIn) , Allgäuer, Michael (VerfasserIn) , Neumann, Olaf (VerfasserIn) , Budczies, Jan (VerfasserIn) , Rempel, Eugen (VerfasserIn) , Horak, Peter (VerfasserIn) , Glade, Julia (VerfasserIn) , Goldschmid, Hannah (VerfasserIn) , Şeker-Cin, Huriye (VerfasserIn) , Brandt, Regine (VerfasserIn) , Kriegsmann, Mark (VerfasserIn) , Leichsenring, Jonas (VerfasserIn) , Winter, Hauke (VerfasserIn) , Faehling, Martin (VerfasserIn) , Fischer, Jürgen (VerfasserIn) , Heußel, Claus Peter (VerfasserIn) , Herth, Felix (VerfasserIn) , Brummer, Tilman (VerfasserIn) , Fröhling, Stefan (VerfasserIn) , Schirmacher, Peter (VerfasserIn) , Thomas, Michael (VerfasserIn) , Endris, Volker (VerfasserIn) , Penzel, Roland (VerfasserIn) , Kazdal, Daniel (VerfasserIn) , Bochtler, Tilmann (VerfasserIn) , Stenzinger, Albrecht (VerfasserIn)
Dokumenttyp: Article (Journal)
Sprache:Englisch
Veröffentlicht: 19 February 2021
In: Lung cancer
Year: 2021, Jahrgang: 154, Pages: 131-141
ISSN:1872-8332
DOI:10.1016/j.lungcan.2021.02.022
Online-Zugang:Verlag, lizenzpflichtig, Volltext: https://doi.org/10.1016/j.lungcan.2021.02.022
Verlag, lizenzpflichtig, Volltext: https://www.sciencedirect.com/science/article/pii/S0169500221000829
Volltext
Verfasserangaben:Anna-Lena Volckmar, Petros Christopoulos, Martina Kirchner, Michael Allgäuer, Olaf Neumann, Jan Budczies, Eugen Rempel, Peter Horak, Julia Glade, Hannah Goldschmid, Huriye Seker-Cin, Regine Brandt, Mark Kriegsmann, Jonas Leichsenring, Hauke Winter, Martin Faehling, Jürgen R. Fischer, Claus Peter Heußel, Felix Herth, Tilman Brummer, Stefan Fröhling, Peter Schirmacher, Michael Thomas, Volker Endris, Roland Penzel, Daniel Kazdal, Tilmann Bochtler, Albrecht Stenzinger
Beschreibung
Zusammenfassung:Objectives - Implementation of tyrosine kinase inhibitors (TKI) and other targeted therapies was a main advance in thoracic oncology with survival gains ranging from several months to years for non-small-cell lung cancer (NSCLC) patients. High-throughput comprehensive molecular profiling is of key importance to identify patients that can potentially benefit from these novel treatments. - Material and Methods - Next-generation sequencing (NGS) was performed on 4500 consecutive formalin-fixed, paraffin-embedded specimens of advanced NSCLC (n=4172 patients) after automated extraction of DNA and RNA for parallel detection of mutations and gene fusions, respectively. - Results and Conclusion - Besides the 24.9 % (n=1040) of cases eligible for approved targeted therapies based on the presence of canonical alterations in EGFR exons 18-21, BRAF, ROS1, ALK, NTRK, and RET, an additional n=1260 patients (30.2 %) displayed rare or non-canonical mutations in EGFR (n=748), BRAF (n=135), ERBB2 (n=30), KIT (n=32), PIK3CA (n=221), and CTNNB1 (n=94), for which targeted therapies could also be potentially effective. A systematic literature search in conjunction with in silico evaluation identified n=232 (5.5 %) patients, for which a trial of targeted treatment would be warranted according to available evidence (NCT level 1, i.e. published data showing efficacy in the same tumor entity). In conclusion, a sizeable fraction of NSCLC patients harbors rare or non-canonical alterations that may be associated with clinical benefit from currently available targeted drugs. Systematic identification and individualized management of these cases can expand applicability of precision oncology in NSCLC and extend clinical gain from established molecular targets. These results can also inform clinical trials.
Beschreibung:Gesehen am 27.05.2021
Beschreibung:Online Resource
ISSN:1872-8332
DOI:10.1016/j.lungcan.2021.02.022

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