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Pneumologie 2018; 72(11): 774-781
DOI: 10.1055/a-0647-9835
Übersicht
© Georg Thieme Verlag KG Stuttgart · New York

Strategien zur Überwindung der erworbenen EGFR-TKI-Resistenz durch T790M spezifische Substanzen am Beispiel von Osimertinib

Strategies to Overcome Acquired Resistance to EGFR-TKI Therapy Based on T790M Specific Substances using Osimertinib as an Example
F. Griesinger
 1   Klinik für Hämatologie und Onkologie, Pius-Hospital Oldenburg, Universitätsmedizin Oldenburg, Universitätsklinik Innere Medizin – Onkologie, Oldenburg
,
S. Radke
 2   AstraZeneca, Medical Affairs, Wedel
,
A. Lüers
 1   Klinik für Hämatologie und Onkologie, Pius-Hospital Oldenburg, Universitätsmedizin Oldenburg, Universitätsklinik Innere Medizin – Onkologie, Oldenburg
,
B. Deschler-Baier
 3   Comprehensive Cancer Center Mainfranken, Universitätsklinikum Würzburg, Würzburg
,
M. Kimmich
 4   Abteilung für Pneumologie und Pneumologische Onkologie, Robert-Bosch-Krankenhaus Klinik Schillerhöhe, Gerlingen
,
M. Sebastian
 5   Abteilung für Hämatologie und Onkologie, Universitätsklinikum Frankfurt, Frankfurt/Main
,
C. Schulz
 6   Klinik und Poliklinik für Innere Medizin II, Universitätsklinikum Regensburg, Regensburg
,
W. Brugger
 7   Medizinische Klinik II, Hämatologie/Onkologie, Schwarzwald-Baar Klinikum, Akad. Lehrkrankenhaus der Univ. Freiburg, Villingen-Schwenningen
,
R. Wiewrodt
 8   Medizinische Klinik A, Universitätsklinikum Münster, Münster
,
R. Pirker
 9   Klinische Abteilung für Onkologie, Allgemeines Krankenhaus-Universitätskliniken Wien
,
M. Früh
10   Klinik für Hämatologie/Onkologie, Kantonsspital St. Gallen, St. Gallen
,
O. Gautschi
11   Abteilung für Medizinische Onkologie, Kantonsspital Luzern, Luzern
,
J. Wolf
12   Klinik I für Innere Medizin, Centrum für Integrierte Onkologie, Uniklinik Köln, Köln
› Author Affiliations
Further Information

Publication History

eingereicht 18 December 2017

akzeptiert nach Revision 18 June 2018

Publication Date:
08 November 2018 (online)

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Zusammenfassung

Die Resistenzbildung gegenüber der 1. und 2. Generation von Tyrosinkinase-Inhibitoren (TKIs) des epidermalen Wachstumsfaktors (EGFR) stellt bei der Behandlung von Patienten mit nicht kleinzelligem Lungenkarzinom, die eine aktivierende Mutation im EGFR aufweisen, ein großes Problem dar. Drittgenerations-EGFR-TKIs richten sich sowohl gegen aktivierende als auch gegen die Resistenz-vermittelnde T790M-Mutation. EGFR-TKIs der 3. Generation zeigen in klinischen Studien bei T790M-positiven Patienten relevante Wirksamkeit bei meist milden bis moderaten klassenspezifischen Nebenwirkungen. Molekularpathologischen Analysen kommt bei der Entscheidung zur Therapie mit Drittgenerations-EGFR-TKIs eine bedeutsame Rolle zu. In dieser Übersichtsarbeit wird der aktuelle Entwicklungsstand von Drittgenerations-EGFR-TKIs dargestellt mit einem Schwerpunkt auf Osimertinib, dem ersten und bislang einzigen in Deutschland zugelassenen Wirkstoff dieser Klasse. Zudem wird die Relevanz einer molekularen Diagnostik an Tumorgewebe bzw. an zirkulierender Tumor-DNA diskutiert.

Abstract

Tyrosine kinase inhibitors (TKIs) of the epidermal growth factor receptor (EGFR) are widely used in non-small cell lung cancer patients harboring activating EGFR mutations. However, resistance mechanisms, particularly the T790 M mutation, hamper longer-term therapeutic success of first and second generation EGFR-TKIs. To address this unmet medical need, EGFR-TKIs of the third generation are under clinical development. Relevant clinical efficacy with mainly mild to moderate class-specific side effects has been shown for third-generation EGFR-TKIs. Molecular testing is of major importance in deciding for treatment with third generation EGFR-TKIs. This article elucidates the developmental state of third generation EGFR-TKIs with its focus on Osimertinib, the first and currently the only compound in this class which is approved in Germany. Additionally, the medical importance of molecular diagnosis using tumor tissue and circulating tumor DNA is discussed.

 

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