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TumorDiagnostik & Therapie 2024; 45(03): 161-177
DOI: 10.1055/a-2241-7192
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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 wird zwischen einer lokalen und einer metastasierten Tumorerkrankung unterschieden. Neue Behandlungsverfahren wie Immuntherapie und zielgerichtete Therapie halten in beiden Fällen Einzug in die derzeitigen Therapiestrategien und verbessern damit die Prognose der Patient*innen.

Kernaussagen

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

  • Erste Studien (DANTE, MATTERHORN, KEYNOTE-585, NEONIPIGA, INFINITY) zeigen v.a. 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 Therapie Trastuzumab kombiniert werden. Seit der KEYNOTE-811 sollte die Therapie bei zusätzlich PD-L1-positiven Tumoren (CPS ≥1) um Pembrolizumab ergänzt werden. Für die Zweitlinie steht Trastuzumab-Deruxtecan zur Verfügung.

  • Metastasierte Magenkarzinome mit CPS-Score ≥5 werden mit FOLFOX und Nivolumab behandelt. Seit Kurzem stellt bereits ab einem CPS ≥1 Pembrolizumab in der Erstlinie in Kombination mit Chemotherapie bei HER2-negativen, PD-L1-positiven Magenkarzinomen eine Therapieoption dar. Weitere Studien bekräftigen den Stellenwert der Immunchemotherapie in dieser Indikation.

  • Die Zweitlinientherapie wird anhand der Vortherapien, dem Allgemeinzustand der Patient*innen sowie der molekularen Stratifizierung (HER2 und MSI-H) ausgewählt. 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 u.a. eine orale Therapieoption etabliert.

  • Für den gegen CLDN18.2 gerichteten Antikörper Zolbetuximab wird in diesem Jahr die Zulassung für CLDN18.2-positive Tumoren in Kombination mit Chemotherapie erwartet.

  • Das Target FGFR2b befindet sich in der klinischen Entwicklung – Phase-II-Daten sind vielversprechend.

Schlüsselwörter

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


Publication History

Article published online:
27 March 2024

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