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Gastroenterologie up2date 2023; 19(03): 261-278
DOI: 10.1055/a-1984-6886
Ösophagus/Magen/Duodenum

Medikamentöse Therapiestrategien des Magenkarzinoms

Magdalena Scheck
,
Sylvie Lorenzen
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Magenkarzinome sind in Deutschland bei Frauen für 2,4% und bei Männern für 3,5% der Krebsneuerkrankungen verantwortlich und gehen mit einer hohen Letalitätsrate einher. In der Therapie unterscheidet man zwischen einer lokalen und einer metastasierten Tumorerkrankung. Neue Verfahren wie Immuntherapie und zielgerichtete Therapie halten in beiden Fällen Einzug in die derzeitigen Therapiestrategien und verbessern die Prognose der Patient*innen.
Kernaussagen

  • Nicht metastasierte Adenokarzinome werden kurativ therapiert. Ab einem Stadium von T3 und/oder N+ sollte eine perioperative Chemotherapie mit FLOT sowie eine onkologische Resektion stattfinden. Bei T2, N0 kann eine perioperative Chemotherapie erfolgen.

  • Erste Studien (DANTE, NEONIPIGA, INFINITY) zeigen vor allem in immunogenen Tumoren (hoher CPS-Score und MSI-H) eine vielversprechende Verbesserung der pCR-Raten, wenn perioperativ eine Immuntherapie (ICI) eingesetzt wird. Ähnliches gilt für zielgerichtete Therapien gegen HER2, auch wenn das Toxizitätsprofil noch nicht ganz geklärt ist. Diese Ansätze könnten in Zukunft die Prognose resektabler Magenkarzinome weiter verbessern.

  • Bei metastasierten Magenkarzinomen erfolgt eine Stratifizierung anhand molekularer Marker (MSI, HER2, PD-L1-Status).

  • In der Erstlinie für HER2-positive metastasierte Magenkarzinome sollte die Standardchemotherapie (FOLFOX/CAPOX) mit der anti-HER2-gerichteten Trastuzumab-Therapie kombiniert werden. Für die Zweitlinie wurde kürzlich Trastuzumab-Deruxtecan durch die EMA zugelassen. Erste Ansätze (KEYNOTE-811) erweitern die HER2-gerichtete Therapie um ICI.

  • Metastasierte Magenkarzinome mit CPS-Score ≥ 5 werden mit FOLFOX und Nivolumab behandelt. Weitere Studien bestätigen den Stellenwert der Immunchemotherapie in diesen Fällen.

  • Die Zweitlinientherapie erfolgt anhand der Vortherapien, dem Allgemeinzustand der Patient*innen sowie der molekularen Stratifizierung (HER2 und MSI-H). Mikrosatelliteninstabile (MSI/dMMR) Magenkarzinome zeigen eine erhöhte Sensibilität für ICI. Eine Zulassung für Pembrolizumab ab der Zweitlinie besteht seit 2022.

  • Für die Drittlinie ist mit TAS-102 unter anderem eine orale Therapieoption etabliert.

  • Weitere vielversprechende zielgerichtete Therapien (gegen CLDN18.2 und FGFR2b) befinden sich in der Entwicklung.

Schlüsselwörter

Magenkarzinom - perioperative Chemotherapie - palliative Chemotherapie - Immuntherapie - zielgerichtete Therapie


Publikationsverlauf

Artikel online veröffentlicht:
13. September 2023

© 2023. Thieme. All rights reserved.

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