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Personalisierte Therapie beim metastasierten Urothelkarzinom – Vision oder Wirklichkeit?

Personalized treatment of metastatic urothelial cancer—Vision or reality?

Zusammenfassung

Hintergrund

Über viele Jahre war die personalisierte Therapie beim metastasierten Urothelkarzinom (mUC) kein Thema von Klinik und Forschung. In den letzten Jahren hat sich dies gewandelt und Gensequenzierung sowie Entwicklung von prädiktiven Biomarkern hat auch beim UC an Bedeutung gewonnen. FGFR2/3(„fibroblast growth factor receptor“)-Alterationen haben sich als Tumortreiber etabliert und die Patientenselektion nach FGFR-Mutationen oder Fusionen wird bereits in den europäischen Leitlinien der onkologischen und urologischen Gesellschaften erwähnt.

Ziel der Arbeit

Ziel dieser narrativen Übersichtsarbeit ist die Darstellung der aktuellen Datenlage und die klinische Bedeutung der personalisierten Therapie beim metastasierten UC.

Material und Methoden

Es wurde kein systematisches Review durchgeführt.

Ergebnisse

Patienten mit selektiven Alterationen sollten in Studien eingeschlossen werden oder im Sinne von individuellen Therapieversuchen nach Beschluss des molekularen Tumorboards behandelt werden. Die Daten des in den USA bereits zugelassenen FGFR-Inhibitors Erdafitinib zeigen eine Ansprechrate von 40 % bei vorbehandelten Patienten. Andere Mutationen, wie zum Beispiel am BRCA1/2-Gen oder TSC1, könnten ebenfalls therapeutisch wegweisend sein. Der klinische Beweis dafür steht jedoch noch aus. Studien bei genomisch selektierten Patienten mit Monotherapien oder Kombinationen bei therapienaiven und vorbehandelten Patienten laufen und werden über weitere künftige Therapieoptionen und -strategien mehr Aufschluss geben.

Schlussfolgerung

Die personalisierte Therapie beim metastasierten UC ist ein vielversprechender, effektiver Therapieansatz bei selektierten Patienten und verbessert die seit Jahren stagnierende Prognose von UC-Patienten.

Abstract

Background

For many years personalized treatment of metastatic urothelial cancer (mUC) was not a priority topic in clinical treatment and research. This has changed in recent years and gene sequencing as well as the development of predictive biomarkers have also become important for UC. Alterations in fibroblast growth factor receptor 2/3 (FGFR2/3) have become established as tumor drivers and patient selection according to FGFR mutations and fusions is already included in the European guidelines of oncological and urological societies.

Objective

The aim of this narrative review is the presentation of the current data situation and the clinical relevance of personalized treatment for mUC.

Material and methods

No systematic review was performed.

Results

Patients with selective alterations should be included in studies or treated in the sense of individual treatment attempts according to the decision of the molecular tumor board. The data of the FGFR inhibitor erdafitinib, which has already been approved in the USA, show a response rate of 40% in pretreated patients. Other mutations, such as in the BRCA1/2 gene or TSC1, could also be therapeutically groundbreaking; however, the clinical evidence for this is still lacking. Studies involving genomically selected patients with monotherapy or combinations in treatment naïve and pretreated patients are currently ongoing and will provide more information about future treatment options and strategies.

Conclusion

Personalized treatment for mUC in selected patients is a promising and effective approach and will improve the prognosis of UC patients, which has stagnated for many years.

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Correspondence to Maria De Santis.

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Interessenkonflikt

M. De Santis weist auf folgende Beziehungen hin: Honorare, Beratungstätigkeit: AAA, Amgen, Astellas, AstraZeneca, Basilea, Bayer, Bioclin, BMS, EISAI, Ferring, Immunomedics, Ipsen, Janssen, MSD, Merck, Novartis, Pfizer, Roche, Sandoz, Sanofi, SeaGen. R. Tahbaz weist auf folgende Beziehungen hin: Astellas, EISAI, Ipsen, MSD, Pfizer.

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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Tahbaz, R., De Santis, M. Personalisierte Therapie beim metastasierten Urothelkarzinom – Vision oder Wirklichkeit?. Onkologie 28, 805–811 (2022). https://doi.org/10.1007/s00761-022-01218-4

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  • DOI: https://doi.org/10.1007/s00761-022-01218-4

Schlüsselwörter

  • Mikrosatelliteninstabilität
  • Präzisionsmedizin
  • Immuntherapie
  • Fibroblastenwachstumsfaktor-Rezeptoren
  • Biomarker

Keywords

  • Microsatellite instability
  • Precision medicine
  • Immunotherapy
  • Receptors, fibroblast growth factor
  • Biomarkers