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Aktuelle Urol 2022; 53(05): 403-415
DOI: 10.1055/a-1579-0562
Übersicht

Interdisziplinäre Empfehlungen zur Behandlung des fortgeschrittenen Nierenzellkarzinoms

Interdisciplinary recommendations for the treatment of advanced renal cell carcinoma
Kurt Miller
1   Urologie, Charité – Universitätsmedizin Berlin, Berlin, Germany
,
Lothar Bergmann
2   Ambulantes Krebszentrum Schaubstraße (AKS), Frankfurt, Germany
,
Christian Doehn
3   Urologikum Lübeck, Lübeck, Germany
,
Viktor Grünwald 
4   Urologie, Universität Duisburg-Essen, Essen, Germany (Ringgold ID: RIN27170)
,
Jürgen E. Gschwend
5   Urologie, Klinikum rechts der Isar, Technische Universität München, München, Germany
,
Philipp Ivanyi
6   Urologie, Medizinische Hochschule Hannover, Hannover, Germany (Ringgold ID: RIN9177)
,
Markus A. Kuczyk
6   Urologie, Medizinische Hochschule Hannover, Hannover, Germany (Ringgold ID: RIN9177)
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Zusammenfassung

In den letzten zwei Jahren sind Anti-VEGFR-Tyrosinkinase-Inhibitoren (TKI) in der Erstlinientherapie des fortgeschrittenen Nierenzellkarzinom nahezu komplett durch Immuntherapie-Kombinationen mit Checkpoint-Inhibitoren ersetzt worden. Die Prognose der Patienten konnte damit nochmals deutlich verbessert werden. In den entsprechenden Zulassungsstudien wurden mediane Überlebenszeiten von drei bis vier Jahren erreicht. Die TKI-Monotherapie hat bei günstigem Progressionsrisiko, bei Kontraindikationen gegen eine Immuntherapie und im Kontext der SARS-CoV-2-Pandemie aber weiterhin einen Stellenwert.

Die Frage, welche Therapie für welche Patient/-innen geeignet ist, stellt sich vor dem Hintergrund von zwei CPI-TKI-Kombinationen und einer reinen CPI-Kombination als neuem Erstlinien-Standard auf einer neuen Basis. Temsirolimus und die Kombination Bevacizumab + Interferon-alpha spielen nahezu keine Rolle mehr. In der Zweitlinientherapie wurde für Nivolumab und Cabozantinib nach TKI-Vortherapie ein signifikanter Überlebensvorteil gegenüber Everolimus gezeigt. Die Kombination Lenvatinib + Everolimus sowie Axitinib sind weitere zugelassene Substanzen. Auch für TKI liegen Daten vor, allerdings mit begrenzter Aussagekraft. Everolimus als Monotherapie ist durch die neuen Optionen in der Zweitlinie abgelöst worden. Insgesamt fehlt es an Biomarkern, die bei der Therapiewahl unterstützen könnten. Die kürzlich erfolgte Aktualisierung der S3-Leitlinie war daher ein wichtiger Schritt, um evidenzbasiert in der klinischen Praxis Orientierung zu geben.

Bei potenziell komplexeren Therapiealgorithmen und gleichzeitig nur wenig Evidenz muss auch die Frage nach der optimalen Sequenztherapie neu diskutiert werden. Die meisten Zweitlinien-Optionen wurden nach Versagen einer gegen VEGF-gerichteten TKI-Therapie geprüft, die nur noch für eine Minderheit der Patient/-innen infrage kommt.

Im Rahmen eines interdisziplinären Expertengesprächs wurden im November 2020 die aktuelle Datenlage einschließlich neuerer Studienergebnisse sowie relevante Kriterien für die individuelle Therapieentscheidung diskutiert. Auch die SARS-CoV-2-Pandemie fand dabei Berücksichtigung. Ziel war es, gemeinsame Empfehlungen auf Basis der aktuell publizierten Daten und der eigenen klinischen Erfahrung für den Praxisalltag abzuleiten. Die Ergebnisse werden in dieser Publikation vorgestellt.

Abstract

In the treatment of advanced renal cell carcinoma, anti-VEGFR tyrosine kinase inhibitors (TKI) have been replaced mostly by immunotherapy combinations with checkpoint inhibitors (CPI), especially in first line therapy. Due to these novel therapies, the prognosis of patients has been improved further. In pivotal studies a median overall survival of 3–4 years has been achieved. TKI monotherapy remains important for patients with low risk, a contraindication against immunotherapy and with regard to the SARS-CoV-2 pandemic.

Selection of the correct first line therapy is difficult to answer because there are two CPI-TKI combinations and one CPI-combination. Temsirolimus and the combination bevacizumab + interferon alfa have become less important. In second line therapy, nivolumab and cabozantinib have demonstrated superior overall survival compared to everolimus. Furthermore, the combination of lenvatinib + everolimus and axitinib are approved treatment options in the second line and further settings. TKI are an option as well, but they have lower supporting evidence. Everolimus has been replaced in the second line setting by these new options. Biomarkers are not available. The German S3 guideline has been updated recently to give better orientation in clinical practice.

The question of the optimal sequence is still unanswered. Most second line options were evaluated after failure of anti-VEGF-TKI, but these are only applicable for a minority of patients.

The purpose of an interdisciplinary expert meeting in november 2020 was to debate which criteria should influence the therapy. The members discussed several aspects of treating patients with advanced or metastatic RCC, including the SARS-CoV-2 pandemic. As in previous years, the experts intended to provide recommendations for clinical practice. The results are presented in this publication.

Schlüsselwörter

Nierenzellkarzinom - Systemtherapie - Metastasen - Immuntherapie - Checkpoint-Inhibitor

Keywords

Renal cell cancer - Metastases - Immunotherapy - Checkpoint-inhibitor - medical treatment


Publication History

Received: 15 March 2021

Accepted after revision: 02 August 2021

Article published online:
01 December 2021

© 2021. Thieme. All rights reserved.

Georg Thieme Verlag KG
Rüdigerstraße 14, 70469 Stuttgart, Germany

 

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