Immuncheckpointinhibition beim metastasierten Urothelkarzinom

Zusammenfassung

Die Behandlung des metastasierten Urothelkarzinoms (mUC) erfolgte standardmäßig durch die Applikation chemotherapiehaltiger Regime. Während in der Erstlinienbehandlung durch cisplatinbasierte Kombinationen noch relativ gute Ansprechraten und eine Verlängerung des Gesamtüberlebens erzielt werden kann, verringert sich dieses in der platinrefraktären Situation und wenn − aufgrund einer eingeschränkten Nierenfunktion oder Komorbiditäten − kein Cisplatin mehr gegeben werden kann. Die neue Substanzklasse der Immuncheckpointinhibitoren (ICI) hat die Therapie beim mUC deutlich verbessert, sowohl nach platinhaltiger Therapie als auch bei cisplatin-ungeeigneten Patienten. Aktuell sind durch die EMA Atezolizumab, Nivolumab und Pembrolizumab basierend auf Phase II- und III-Daten für die Therapie des mUC zugelassen. Zukünftige Entwicklungen fokussieren auf die Anwendung in der Erstlinie und der adjuvanten Therapie, auch in der Kombination von PD-L1-/PD-1-Antikörpern mit zusätzlichen ICI-Targets und der Kombination mit Chemotherapie. Klinischer Bedarf besteht in der Etablierung von Biomarkern in der ICI-Therapie, da die derzeitigen Ergebnisse für den PD-L1-Status heterogen sind.

Abstract

The treatment of metastatic urothelial carcinoma is characterized by the administration of combinatory regimes of chemotherapy. In the first-line treatment theses regimes demonstrate relatively good objective response rates and prolongation of overall survival. The prognosis declines if the patient is refractory to platin in the second- or third-line treatment or if the patient is ineligible for cisplatin in the first-line setting. Cisplatin ineligibility is defined by a poor renal function or subsequent comorbidities. The new class of immune checkpoint inhibitors (ICI) has led to an impressive improvement in the therapy of mUC in platin-refractory or cisplatin-ineligible patients. Currently, the EMA has approved Atezolizumab, Nivolumab and Pembrolizumab based on phase II and III trial data. Future developments focus on first-line and adjuvant treatment of ICI with PD-L1/PD-1 as a backbone and in combination with either other ICI or chemotherapy. The prognostic use of biomarkers in ICI is still a medical need as the currently available results with regard to the PD-L1 status are heterogeneous.

Schlüsselwörter

Urothelkarzinom - Immuncheckpointinhibition - PD1 - PD-L1 - Atezolizumab

Keywords

urothelial carcinoma - immune checkpoint inhibition - PD1 - PD-L1 - Atezolizumab

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