Was ist neu beim Magenkarzinom?

Was ist neu?

Therapie des lokal fortgeschrittenen Adenokarzinoms des Magens und AEG Im lokal fortgeschrittenen Stadium werden multimodale Therapien wie die perioperative Chemotherapie mit FLOT oder die neoadjuvante Radiochemotherapie in nationalen und internationalen Leitlinien empfohlen. Die Integration der Immuntherapie in diese Konzepte hat das Potenzial, die Prognose wesentlich zu verbessern. Phase-II/III-Studien wie die DANTE-, die KEYNOTE-585- und die MATTERHORN-Studie zeigen ermutigende Ergebnisse hinsichtlich verbesserter pathologischer Remissionen, jedoch sind Daten zur Überlebenszeitverlängerung für unselektionierte Patienten bislang ernüchternd.

Neuartige Behandlungskonzepte für die palliative Therapie In der palliativen Therapie des metastasierten Magenkarzinoms bieten Immuntherapien und neue zielgerichtete Antikörpertherapien Hoffnung. Studien wie CheckMate-649 und KEYNOTE-859 zeigen eine Verbesserung des Überlebens und der Ansprechraten. Aktuell bestehen sowohl für Pembrolizumab als auch Nivolumab Zulassungen in der Erstlinienbehandlung von Tumoren mit positiver PD-L1-Expression. Bei HER2-positiven Tumoren konnte in der KEYNOTE-811-Studie gezeigt werden, dass Patienten von Kombinationstherapien mit Immuncheckpoint-Inhibition und anti-HER2-Therapien profitieren. Das Antikörper-Wirkstoff-Konjugat Trastuzumab-Deruxtecan ist eine vielversprechende Zweitlinien-Therapieoption für HER2-positive Tumore nach Therapieversagen mit Trastuzumab. Darüber hinaus zeigt der bispezifische Antikörper Zanidatamab vielversprechende Ergebnisse in der Erstlinienbehandlung. Neue zielgerichtete Therapien gegen CLDN18.2 und FGFR2b zeigen vielversprechende Daten. Der gegen Claudin 18.2 (CLDN18.2) gerichtete Antikörper Zolbetuximab führt bei Patienten mit CLDN18.2-positiver Erkrankung in der Erstlinientherapie zu einer Verbesserung des Überlebens, im Vergleich zu Chemotherapie allein, sodass eine Zulassung 2024 erwartet wird.

Abstract

In the locally advanced stage, multimodal therapies such as perioperative chemotherapy with FLOT or neoadjuvant radiochemotherapy are recommended. The integration of immunotherapy into these concepts could improve the prognosis. Phase II/III trials such as DANTE, KEYNOTE-585 and MATTERHORN show promising results in terms of pathological remissions but data on survival time extension for unselected patients are so far sobering. Immunotherapies and new targeted therapies offer hope in the palliative treatment of metastatic gastric cancer. Studies such as CheckMate-649 and KEYNOTE-859 show an improvement in survival and response rates. Currently, both pembrolizumab and nivolumab have been approved for the first-line treatment of tumors with positive PD-L1 expression. In HER2-positive tumors, the KEYNOTE-811 study showed that patients benefit from combination therapies with immune checkpoint inhibition and anti-HER2 therapies. The antibody-drug conjugate trastuzumab-deruxtecan is a promising second-line treatment option for HER2-positive tumors after treatment failure with trastuzumab.

In addition, the bispecific antibody zanidatamab shows promising results in first-line treatment. New targeted therapies against CLDN18.2 and FGFR2b are showing promising results. The anti-claudin 18.2 (CLDN18.2) antibody zolbetuximab leads to improved survival compared to chemotherapy alone in patients with CLDN18.2 positive disease in first-line therapy, with approval expected in 2024.

Schlüsselwörter

gastroösophageles Adenokarziom - Adenokarzinom des Magens - zielgerichtete Therapie - Immuntherapie - Checkpoint-Inhibition

Keywords

gastroesophageal adenocarcinoma - adenocarcinoma of the stomach - targeted therapy - immunotherapy - checkpoint inhibition

Publikationsverlauf

Artikel online veröffentlicht:
15. August 2024

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