Immuntherapie im unteren Gastrointestinaltrakt

Immunotherapy in lower gastrointestinal cancer

Zusammenfassung

Hintergrund

Die Immuntherapie ist von zunehmender Bedeutung bei vielen Krebserkrankungen. In den letzten Monaten erfolgten erste Zulassungen auch bei gastrointestinalen Tumoren.

Ziel der Arbeit

Die Übersicht soll den aktuellen Stellenwert von Inhibitoren gegen „programmed cell death protein 1“ (PD-1)/„programmed cell death ligand 1“ (PD-L1) und „cytotoxic T‑lymphocyte-associated protein 4“ (CTLA4) in der Therapie der unteren gastrointestinalen Tumoren beleuchten.

Material und Methoden

Publikationen aus MEDLINE® (U.S. National Library of Medicine®, Bethesda, MD, USA), der American Society of Clinical Oncology (ASCO) und der European Society for Medical Oncology (ESMO) aus den Jahren 2012–2020 wurden systematisch gesammelt und ausgewertet.

Ergebnisse

Die PD-1/-L1- und die CTLA4-Inhibition sind beim kolorektalen Karzinom (KRK) in kleinen, durch eine hohe Tumorlast gekennzeichneten Subgruppen mit defizientem „mismatch repair“ (dMMR) bzw. bei mikrosatelliteninstabilen (MSI-H-)Tumoren oder bei Tumoren mit Mutationen in der „polymerase epsilon proofreading domain“ (POLE) von Relevanz. Mit Pembrolizumab liegt die erste zugelassene Immuntherapie in der Erstlinientherapie des dMMR/MSI‑H KRK vor. Laufende Studien untersuchen den Einsatz der Immuntherapie in diesen Subgruppen in der (neo-)adjuvanten Situation. Jenseits dieser definierten Subgruppen sind die Ergebnisse aus Studien bislang nicht eindeutig. Beim Analkarzinom ist eine moderate immuntherapeutische Wirksamkeit in der fortgeschrittenen Situation gezeigt.

Diskussion

Die Hoffnung liegt auf laufenden Studienkonzepten, die mit Kombinationen und sequenziellen biomarkerbasierten Ansätzen die Immuntherapien einer größeren Gruppe der Patienten mit KRK zugänglich machen könnten.

Abstract

Background

Immunotherapy has gained increasing importance in the management of a variety of cancers. In recent months, the first agents were approved for gastrointestinal cancers.

Objectives

This review will highlight the current role of programmed cell death protein 1 (PD-1)/programmed cell death ligand 1 (PD-L1) and cytotoxic T‑lymphocyte-associated protein 4 (CTLA4) inhibitors in lower gastrointestinal cancers.

Materials and methods

Publications from MEDLINE® (U.S. National Library of Medicine®, Bethesda, MD, USA), American Society of Clinical Oncology (ASCO) and European Society for Medical Oncology (ESMO) from 2012–2020 were collected and evaluated.

Results

The relevance of PD-1/-L1 and CTLA4 inhibitors in colorectal cancer (CRC) is currently limited to small subgroups defined by a high tumor mutational burden (deficient mismatch repair [dMMR]/microsatellite instable [MSI-H] tumors or polymerase epsilon proofreading domain [POLE] mutated). Pembrolizumab is the first approved agent for first-line treatment of dMMR/MSI‑H CRC. Ongoing trials evaluated the role of immunotherapy in the neo-adjuvant setting. Beyond these defined subgroups, results from studies have been inconclusive to date. In advanced anal cancer, PD-1/L1 inhibition shows moderate efficacy.

Discussion

Ongoing trials evaluating combinations or sequential regimen with biomarker-based approaches may enable larger groups of patients access to immunotherapy.

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Correspondence to Alexander Stein.

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Interessenkonflikt

A. Stein gibt institutionelle Forschungsunterstützung von BMS und Merck sowie Honorare für die Teilnahme an Advisory Boards oder für Vorträge von Astra Zeneca, BMS, Merck, MSD und Roche an.

Für diesen Beitrag wurden von den Autoren keine Studien an Menschen oder Tieren durchgeführt. Für die aufgeführten Studien gelten die jeweils dort angegebenen ethischen Richtlinien.

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T. Seufferlein, Ulm

N. P. Malek, Tübingen

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Stein, A. Immuntherapie im unteren Gastrointestinaltrakt. Gastroenterologe 16, 257–263 (2021). https://doi.org/10.1007/s11377-021-00534-2

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Schlüsselwörter

  • Kolorektales Karzinom
  • Analkarzinom
  • Mikrosatelliteninstabilität
  • Immuncheckpointinhibitoren
  • PD-1-Rezeptor

Keywords

  • Colorectal neoplasms
  • Anus neoplasms
  • Microsatellite instability
  • Immune checkpoint inhibitors
  • PD‑1 receptor