State of the Art: onkogen alteriertes nichtkleinzelliges Lungenkarzinom im Stadium IV
Tóm tắt
Das nichtkleinzellige Lungenkarzinom (NSCLC) im Stadium IV wies bis vor 2 Jahrzehnten eine mediane Überlebenszeit von 7–9 Monaten trotz Chemotherapie auf. Aufgrund der rasanten Entwicklungen der letzten Jahre mit der Zulassung von zielgerichteten Therapien und der Implementierung der Immuntherapie ergeben sich für solche Patient*innen vielfältige Behandlungsmöglichkeiten mit einer teilweise deutlichen Verlängerung der Überlebenszeit. Der vorliegende Artikel gibt eine aktuelle Übersicht über die derzeitigen Therapiestandards des NSCLC im Stadium IV, mit klarem Fokus auf molekular stratifizierte Behandlungsoptionen, Resistenzmechanismen und zukünftige Entwicklungen der zielgerichteten Therapie. Es erfolgte eine systematische Literaturrecherche. Um den Patient*innen eine optimale Therapie anbieten zu können, ist eine initiale Testung des Tumors auf molekulare Alterationen zwingend erforderlich. Neben den schon langjährig eingesetzten EGFR- und ALK-Tyrosinkinaseinhibitoren (TKI) sind mittlerweile viele neue Medikamente bei weiteren Mutationen und Alterationen wie KRAS G12C, ROS1, BRAF V600, MET-Exon-14-Skipping, NTRK oder RET zugelassen. Aufgrund der Resistenzmechanismen sowie der unterschiedlichen Wirksamkeit im zentralen Nervensystem (ZNS) ist eine individuelle Therapiestrategie notwendig. Durch konsequentes Testen und nachfolgende zielgerichtete Therapien kann für Patient*innen, deren Tumoren Treibermutationen aufweisen, eine deutliche Verlängerung des Gesamtüberlebens bei verbesserter Lebensqualität erreicht werden. Künftige Entwicklungen fokussieren auf die weitere Individualisierung der zielgerichteten Therapie, die Entwicklung optimaler Therapiesequenzen und die Identifikation neuer Targets.
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