[Paradigm shift in systemic therapy for metastatic urothelial carcinoma-antibody-drug conjugates (ADCs) and fibroblast growth factor receptor (FGFR) inhibitors]
- PMID: 39235511
- DOI: 10.1007/s00120-024-02440-1
[Paradigm shift in systemic therapy for metastatic urothelial carcinoma-antibody-drug conjugates (ADCs) and fibroblast growth factor receptor (FGFR) inhibitors]
Abstract
Background: Patients with locally advanced or metastatic urothelial carcinoma face a poor prognosis. Standard first-line treatment involves platinum-based combinations followed by avelumab maintenance therapy. Follow-up therapies include enfortumab vedotin, vinflunine, and taxanes.
Objective: To analyze new drug combinations in first-line and follow-up treatment for metastatic urothelial carcinoma concerning their clinical relevance, toxicities, and novel treatment sequences.
Materials and methods: Analysis of new study data from EV-302/KN-A39 (enfortumab vedotin and pembrolizumab) and CheckMate-901 (nivolumab and gemcitabine-cisplatin) for untreated metastatic patients as well as TROPHY-U-01 (sacituzumab govitecan) and THOR (erdafitinib) for later lines.
Results: The new standard in first-line treatment for metastatic urothelial carcinoma is the combination of enfortumab vedotin and pembrolizumab. For cisplatin-eligible patients with contraindications to enfortumab vedotin, the combination of nivolumab and gemcitabine-cisplatin offers an alternative. Erdafitinib presents a new biomarker-based option in the follow-up treatment of metastatic urothelial carcinoma.
Conclusion: These novel combinations are revolutionizing the treatment standard for metastatic urothelial carcinoma and necessitate a new approach to managing side effects.
Zusammenfassung: HINTERGRUND: Patienten mit einem lokal fortgeschrittenen oder metastasierten Urothelkarzinom (mUC) haben eine schlechte Prognose. Standard in der Erstlinie ist eine Platin-basierte Kombination, gefolgt von einer Avelumab-Erhaltungstherapie. Zu den Folgetherapien gehören Enfortumab-Vedotin (EV), Vinflunin und Taxane.
Ziel der arbeit: Neue Substanzkombinationen in der Erstlinien- und Folgetherapien des mUC werden hinsichtlich ihrer klinischen Relevanz, Toxizitäten und neuer Therapiesequenz analysiert.
Material und methoden: Neue Studiendaten zu EV-302/KN-A39 (EV und Pembrolizumab) und CheckMate-901 (Nivolumab und Gemcitabin-Cisplatin) für unbehandelte, metastasierte Patienten sowie TROPHY-U-01 (Sacituzumab-Govitecan) und THOR (Erdafitinib) werden für spätere Therapielinien analysiert.
Ergebnisse: Neuer Standard in der Erstlinientherapie für Patienten mit einem mUC ist die Kombination aus EV und Pembrolizumab. Für Cisplatin-geeignete Patienten mit Kontraindikationen gegen EV ist die Kombination aus Nivolumab und Gemcitabin-Cisplatin eine Alternative. Erdafitinib stellt eine neue biomarkerbasierte Option in der Folgetherapie des mUC dar.
Schlussfolgerung: Die neuen Therapiekombinationen revolutionieren den Behandlungsstandard des mUC und machen ein neues Nebenwirkungsmanagement erforderlich.
Keywords: Chemotherapy; First-line treatment; Immune checkpoint inhibitors; Immunotherapy; Sequential therapy.
© 2024. The Author(s), under exclusive licence to Springer Medizin Verlag GmbH, ein Teil von Springer Nature.
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