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Z Gastroenterol 2020; 58(06): 542-555
DOI: 10.1055/a-1071-8322
Originalarbeit
© Georg Thieme Verlag KG Stuttgart · New York

Current status of immunotherapy in gastrointestinal malignancies

Aktueller Stellenwert der Immuntherapie bei gastrointestinalen Tumoren
Sylvie Lorenzen
1   Department of Hematology and Oncology, Klinikum rechts der Isar, Technical University Munich, Germany
,
Florian Lordick
2   University Cancer Center, University Clinic Leipzig, Germany
,
Sven Heiko Loosen
3   University Hospital Aachen, Department of Medicin III, Aachen, Germany
,
Frank Tacke
4   Charité University Medicine Berlin, Department of Hepatology and Gastroenterology, Berlin, Germany
,
Christian Trautwein
5   Department of Medicin III, University Hospital, Aachen, Germany
,
Christoph Roderburg
4   Charité University Medicine Berlin, Department of Hepatology and Gastroenterology, Berlin, Germany
,
Thomas J. Ettrich
6   Department of Internal Medicine I, University of Ulm, Germany
,
Lukas Perkhofer
6   Department of Internal Medicine I, University of Ulm, Germany
,
Anke Reinacher-Schick
7   Ruhr-Universität, Medizinische Klinik, Bochum, Germany
,
Alexander Stein
8   Hämatologisch-Onkologische Praxis Eppendorf, University Cancer Center Hamburg, Germany
› Author Affiliations
Further Information

Publication History

02 October 2019

24 November 2019

Publication Date:
04 February 2020 (online)

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Abstract

Gastrointestinal (GI) malignant neoplasms have a high global incidence and a huge impact on cancer-associated mortality. In the past years, excitement was growing among oncologists and patients alike for the use of immunotherapy, specifically immune checkpoint inhibitors. The approval of several PD-1/PD-L1 and CTLA-4 inhibitors radically changed the treatment landscape in many cancer types and established immune-oncology as a new treatment strategy against cancer. Despite major breakthrough reports, shortcomings of immune checkpoint inhibitors (ICI) have been observed, including primary and acquired treatment resistance, especially in patients receiving ICIs as a single treatment. Several immunotherapies for the treatment of GI tumors have recently emerged; however, checkpoint inhibition has not yet shown similar success in GI malignancies compared to other solid tumors. Various phase I–III trials focusing on immunotherapies for GI tumors have found only moderate to unsatisfactory objective response rates (ORR), ranging between 10 % and 25 %. In particular, negative studies have been reported in gastric and pancreatic cancer. Nevertheless, small subsets of cancers, such as DNA mismatch repair deficient (dMMR)/microsatellite instable (MSI) cancers, among others, seem to benefit from treatment with immune checkpoint inhibition. Routine testing for the rare molecular features that can predict response should be implemented in clinical routine for all GI tumors, and large scale clinical trials to identify predictive biomarkers are needed. This article will address the current use and evidence for immunotherapy in GI malignancies and future trends in this area for clinical practice.

Zusammenfassung

Gastrointestinale (GI) Tumoren haben weltweit eine hohe Inzidenz und tragen wesentlich zur krebsbedingten Mortalität bei. In den vergangenen Jahren entwickelte sich eine wachsende Begeisterung von Onkologen und Patienten für die Immuntherapie, insbesondere mit Checkpointinhibitoren. Die Zulassung verschiedenster PD-1/PD-L1- und CTLA-4-Inhibitoren hat die Behandlungsmöglichkeiten bei diversen Tumorentitäten nachhaltig beeinflusst und die Immuntherapie als neue onkologische Behandlungsstrategie etabliert. Trotz bahnbrechender Fortschritte gibt es auch Limitationen der immuncheckpointgerichteten Therapie, wie die primäre und erworbene Resistenz, besonders wenn Checkpointinhibitoren als Monotherapie verabreicht werden. Viele Phase-I- bis -III-Immuntherapiestudien wurden in den letzten Jahren bei GI-Tumoren durchgeführt, allerdings ohne vergleichbare Erfolge zu anderen Tumorentitäten und mit lediglich moderaten Ansprechraten zwischen 10 und 25 %. Insbesondere beim Magen- und Pankreaskarzinom zeigten Studien keinen Vorteil gegenüber den herkömmlichen Therapieoptionen. Dennoch scheinen Subgruppen wie u. a. DNA-mismatch-repair-defiziente (dMMR) oder mikrosatelliteninstabile (MSI-H) Tumoren in besonderem Maße von der Behandlung mit Immuncheckpointinhibitoren zu profitieren. Die routinemäßige Testung auf die bekannten molekularen Veränderungen sollte daher bei allen fortgeschrittenen GI-Tumoren erfolgen. Weitere große Studien zur Identifikation prädiktiver Biomarker werden dringend benötigt. Dieser Artikel fasst den derzeitigen klinischen Stand der Immuntherapie bei GI-Malignomen zusammen und bewertet die laufenden und zukünftigen Entwicklungsprogramme und ihre Umsetzung im klinischen Alltag.

Key words

gastrointestinal malignancies - PD-1/PD-L1 blockade - molecular classification - immune checkpoint inhibitor

Schlüsselwörter

Gastrointestinale Tumore - PD-1/PD-L1 - molekulare Klassifikation - Checkpoint-Inhibitoren
 

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