Stellenwert der Immunonkologie bei der Therapie des Urothelkarzinoms

Zusammenfassung

Im November 2016 wurden Studiendaten zur Zweitlinientherapie des metastasierten Urothelkarzinoms mit dem PD-1-Antikörper Pembrolizumab publiziert, die einen Vorteil im Gesamtüberleben gegenüber einer konventionellen Chemotherapie zeigen. Andere PD-1/PD-L1-Inhibitoren befinden sich in fortgeschrittenen klinischen Studien. Diese Substanzklasse wird ab der für 2017 erwarteten Zulassung in dieser Therapiesituation der neue Standard sein und damit die bisher empfohlene Chemotherapie mit Vinflunin ablösen.

Aktuelle Studien überprüfen derzeit den Einsatz von PD-1/PD-L1 gerichteten Substanzen auch in der Erstlinientherapie des metastasierten Urothelkarzinoms. Dabei werden verschiedene Therapiestrategien verfolgt: Monotherapien mit PD-1/PD-L1-Inhibitoren sowie deren Kombinationen mit CTLA-4-Inhibitoren oder konventioneller Chemotherapie. Erste Studiendaten werden für Ende 2017 erwartet.

Ein neuer Therapieansatz verfolgt den Einsatz von Checkpoint-Inhibitoren in der perioperativen Behandlung bei Patienten mit einem muskelinvasiven Urothelkarzinom nach chirurgischer R0-Resektion (Radikale Zystektomie oder Nephroureterektomie). Zwei internationale Phase-III-Studien überprüfen derzeit eine adjuvante Immuntherapie mit Nivolumab oder Atezolizumab. Die Studienrekrutierung wird voraussichtlich Mitte 2018 beendet sein.

Abstract

Data published in November 2016 showed a significant survival benefit for the PD-1 antibody Pembrolizumab in the second-line treatment of metastatic urothelial cancer in comparison to standard chemotherapy. Other PD-1/PD-L1 antibodies are being tested in advanced clinical trials. This class of substances will become standard of care from the time of their approval which is expected for 2017 and will replace vinflunine, which is currently recommended in the German guideline.

PD-1/PD-L1 directed substances are also being tested as a first line treatment of metastatic urothelial carcinoma. Monotherapy is evaluated as well as combination treatments with CTLA-4 inhibitors of conventional chemotherapy. First data are expected at the end of 2017.

A new strategy is the application of PD-1/PD-L1 directed substances in the perioperative treatment of patients with a muscle-invasive urothelial carcinoma after complete surgical resection (cystectomy or nephroureterectomy). Two international phase III trials evaluate an adjuvant immunotherapy with nivolumab and atezolizumab. Recruitment will be completed in 2018.

Schlüsselwörter

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

Keywords

urothelial cancer - immunotherapy - PD-1/PD-L1 inhibition - combination treatment - chemotherapy

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