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Therapie im Stadium IV des nichtkleinzelligen Lungenkarzinoms mit Treibermutation

Treatment of stage IV non-small cell lung cancer with driver mutations

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Der Onkologe Aims and scope

Zusammenfassung

Hintergrund

Die systemische Therapie des nichtkleinzelligen Lungenkarzinoms (NSCLC) ändert sich aktuell fundamental und mit beeindruckender Dynamik. Patienten mit fortgeschrittener Erkrankung werden aufgrund von Biomarkeranalysen entweder mit Immuntherapie, einer Kombination aus Immun- und Chemotherapie oder mit genetisch stratifizierten Therapien behandelt. Eine besondere Herausforderung stellen erworbene Resistenzen dar. Das zunehmende Verständnis für die molekularen Ursachen der Resistenz ermöglicht die Entwicklung potenterer Inhibitoren.

Ziel

In diesem Review sollen der gegenwärtige Therapiestandard und die aktuellen Entwicklungen der zielgerichteten Therapien für fortgeschrittene NSCLC dargestellt werden.

Material und Methoden

Dieses Review basiert auf der Zusammenfassung und Interpretation von Publikationen zu präklinischen und klinischen Studien im Bereich der zielgerichteten Therapie des fortgeschrittenen NSCLC.

Ergebnisse und Diskussion

Zielgerichtete Therapien gegen aktivierende Mutationen im EGFR- und BRAF-Gen sowie ALK- und ROS1-Fusionen stellen bereits den Erstlinienstandard für etwa 15 % der Patienten mit fortgeschrittenen NSCLC dar. Diese Entwicklung hat in retrospektiven Auswertungen zu einem deutlich verlängerten Überleben in diesen Subgruppen geführt. Für weitere Aberrationen werden zielgerichtete Therapien entwickelt, sodass aktuell für etwa 30 % der Patienten eine zielgerichtete Therapieoption besteht. Inhibitoren der neuen Generation zeichnen sich durch eine hohe Wirksamkeit gegen Tumoren mit erworbener Tyrosinkinaseinhibitor(TKI)-Resistenz und bessere Verträglichkeit aus und werden zunehmend in Erstlinie eingesetzt. Um molekulare Ursachen zu verstehen und die wirksamste Therapie auszuwählen, nimmt die Rebiopsie in der Resistenz einen besonderen Stellenwert ein.

Abstract

Background

Systemic treatment of non-small cell lung cancer (NSCLC) is currently undergoing a paradigmatic change with impressive dynamics. Patients with advanced disease are treated based on the analysis of biomarkers either with immunotherapy, a combination of immunotherapy with chemotherapy or with driver mutation-directed targeted drugs. Treatment of acquired resistance remains a particular challenge. An increasing knowledge of the molecular mechanisms underlying resistance enables the development of more potent inhibitors.

Objective

This review focuses on the state of the art and current developments in targeted therapy of advanced stage NSCLC.

Material and methods

This review is based on the summary and interpretation of publications on preclinical and clinical studies in the field of targeted treatment of advanced NSCLC.

Results and conclusion

Targeted treatments against activating mutations in the EGFR and BRAF genes as well as ALK and ROS1 fusions define the standard first line treatment for approximately 15 % of patients with advanced NSCLC. In retrospective analyses this development has led to a substantially prolonged overall survival in these subgroups. Targeted therapies against further aberrations are in clinical evaluation and a targeted treatment is currently available for approximately 30% of patients. Next generation inhibitors are characterized by a high effectiveness against tumors with acquired resistance to tyrosine kinase inhibitors (TKI) and improved tolerability and are increasingly being used as first line treatment. In order to understand the molecular causes and to select the most effective treatment, rebiopsies play a special role in resistance.

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Authors and Affiliations

  1. Lung Cancer Group Cologne (LCGC) und Klinik I für Innere Medizin, Centrum für Integrierte Onkologie, Uniklinik Köln, Kerpener Str. 62, 50937, Köln, Deutschland

    Sebastian Michels &  Jürgen Wolf

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  1. Sebastian Michels
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Correspondence to Jürgen Wolf.

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Interessenkonflikt

S. Michels erhält finanzielle Unterstützung für Forschunsgvorhaben von Pfizer und Novartis sowie Beraterhonorare von Pfizer, Novartis, Roche und Boehringer Ingelheim. J. Wolf erhält finanzielle Unterstützung für Forschunsgvorhaben von Pfizer, Novartis, Bristol-Myers Squibb und Merck-Sharp & Dohme sowie Beraterhonorare von Pfizer, Novartis, Roche, Boehringer Ingelheim, Abbvie, AstraZeneca, Bristol-Myers Squibb, Chugai, Ignyta, Lilly, Merck-Sharp & Dohme und Roche.

Dieser Beitrag beinhaltet keine von den Autoren durchgeführten Studien an Menschen oder Tieren.

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Michels, S., Wolf, J. Therapie im Stadium IV des nichtkleinzelligen Lungenkarzinoms mit Treibermutation. Onkologe 24, 983–991 (2018). https://doi.org/10.1007/s00761-018-0473-1

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