50 Jahre Systemtherapie des Harnblasenkarzinoms

Zusammenfassung

Dieser Übersichtsartikel stellt die Ergebnisse verschiedener Behandlungskonzepte für das metastasierte Urothelkarzinom in den letzten fünf Jahrzehnten zusammen. Mit der Einführung von verschiedenen Kombinations-Chemotherapien wurde ab Mitte der 80er Jahre eine signifikante Überlebensverlängerung und potenzielle Heilbarkeit auch fortgeschrittener Erkrankungsstadien in dieser Tumorentität postuliert. Vor zwei Jahren wurden Studiendaten zur Zweitlinientherapie des metastasierten Urothelkarzinoms mit dem PD1-Antikörper Pembrolizumab publiziert, die erstmals einen Vorteil im Gesamtüberleben gegenüber einer konventionellen Chemotherapie mit Paclitaxel, Docetaxel oder Vinflunin zeigen. Aktuell wird in randomisierten Phase-3-Studien der Einsatz von PD-1/PD-L1 gerichteten Substanzen auch in der Erstlinientherapie des metastasierten Urothelkarzinoms untersucht. Dabei werden verschiedene Therapiestrategien verfolgt: Monotherapien mit PD-1/PD-L1-Inhibitoren sowie deren Kombinationen mit CTLA-4-Inhibitoren oder konventioneller Chemotherapie. Es liegen bereits Daten aus einarmigen Phase-2-Studien zur Monotherapie vor. Erste Daten aus randomisierten Studien werden im Laufe des Jahres 2019 erwartet.

Abstract

This review summarises the treatment strategies of the last five decades for metastatic urothelial cancer. The introduction of combination chemotherapy in the mid-1980s led to clinically significant response rates and prolonged survival. Two years ago, the results of a phase-3 clinical trial with the PD1 inhibitor pembrolizumab for second-line treatment of metastatic urothelial carcinoma were published. These data were the first to show an overall survival benefit in comparison with a conventional chemotherapy with vinflunine, docetaxel or paclitaxel. Currently, PD1/PD-L1 inhibitors are also tested within randomized phase-3-trials for first-line treatment using different approaches either as a monotherapy or a combination with conventional chemotherapy or CTLA-4 inhibitors. Whereas data from single-arm phase-2 clinical trials have already been published, first phase-3 data are expected in 2019.

Schlüsselwörter

Urothelkarzinom - Immuntherapie - PD-1/PD-L1-Inhibition - Chemotherapie

Keywords

urothelial carcinoma - immunotherapy - chemotherapy - PD-1/PD-L1 inhibition - chemotherapy

• Literatur

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