Enfortumab vedotin plus pembrolizumab (EVP) is the standard first-line treatment for metastatic or locally advanced urothelial carcinoma (m/laUC). Real-world patients frequently present with unfavorable clinical characteristics, raising uncertainty about whether outcomes mirror those of the pivotal EV-302/KEYNOTE-A39 trial. This study assessed effectiveness and safety of EVP in a real-world cohort of patients with m/laUC.
Retrospective multicenter study including patients treated with EVP across 25 German hospitals (between 03/2022 and 08/2025). Treatment delivery and monitoring followed local clinical standards. Adverse events (AEs) were documented per CTCAE v5.0. Responses were assessed locally using RECIST v1.1. Progression-free survival (PFS) and overall survival (OS) were analyzed using Kaplan-Meier methodology.
A total of 468 patients (median age = 69 years) were included. The overall response rate (ORR) was 50.2% (partial response:37.4%, complete response:12.8%). Median PFS was 10.2 months (95%CI,8.0-12.7). 12-month and 24-month OS rates were 71.9% and 60.6%, respectively. ECOG PS 0-1 and occurrence of skin toxicity were associated with improved outcomes. Any-grade AEs occurred in 81.8% and grade ≥ 3 AEs in 35.8%. Peripheral sensory neuropathy and skin toxicity were the most common AEs. Ten treatment-related fatal events were recorded.
EVP demonstrated robust effectiveness and manageable toxicity in a large and diverse real-world cohort including patients with divergent histology. Skin toxicity was associated with superior ORR, PFS, and OS. Our findings support EVP as an effective first-line option for patients with m/laUC treated outside clinical trials.
Cancer immunology, immunotherapy : CII. 2026 Jul 12*** epublish ***
Stefanie Zschäbitz, Irfan Bhatti, Jozefina Casuscelli, Ludwig Otto Pachmayr, Thomas Büttner, Thomas Elegeert, Nina Holzwarth, Severin Rodler, Martin Hennig, Emily Rinderknecht, Muammar Dib, Katrin Schlack, Christopher Darr, Anna-Lisa Volk, Philipp Schmucker, Friedemann Zengerling, Pia Paffenholz, Joschka Heil, Eva Erne, Subhajit Mandal, Frederik Wessels, Thea Maria Busse, Daniel Seidl, Susan Foller, Alexander Höllein, Tim Nestler, Christian Gratzke, Louis Rhode, Jakob Kohler, Günter Niegisch, Anna Katharina Seitz, Julia Heinzelbecker, Niklas Klümper, Margitta Retz, Viktor Grünwald, Can Aydogdu, Marco Julius Schnabel
Department of Medical Oncology, National Center for Tumor Diseases (NCT), Heidelberg University Hospital, Im Neuenheimer Feld 460, 69120, Heidelberg, Germany. ., Department of Medical Oncology, National Center for Tumor Diseases (NCT), Heidelberg University Hospital, Im Neuenheimer Feld 460, 69120, Heidelberg, Germany., Department of Urology, LMU University Hospital, LMU Munich, Munich, Germany., School of Medicine and Health, Department of Urology, Technical University of Munich, TUM University Hospital, Munich, Germany., Department of Urology, University Hospital Bonn (UKB), Bonn, Germany., Department of Urology and Pediatric Urology, Saarland University Medical Center, Saarland University, Homburg, Saar, Germany., Department of Urology and Pediatric Urology, University Hospital Würzburg, Würzburg, Germany., Department of Urology, University Hospital Schleswig Holstein, Kiel, Germany., Hospital Am Urban, Berlin, Germany., Department of Urology, Caritas St. Josef Medical Center, University of Regensburg, Regensburg, Germany., Department of Urology, University Hospital Düsseldorf, Düsseldorf, Germany., Department of Urology, University Hospital Muenster, Muenster, Germany., Department of Urology, German Cancer Consortium (DKTK), University Hospital Essen, Essen, Germany., Department of Urology, University Hospital Magdeburg, Magdeburg, Germany., Department of Urology, University Hospital Freiburg, Freiburg, Germany., Department of Urology Und Paediatric Urology, Hospital University of Ulm, Ulm, Germany., Department of Urology, Uro-Oncology, Robot Assisted and Reconstructive Urologic Surgery, University of Cologne, Faculty of Medicine and University Hospital Cologne, Cologne, Germany., Department of Hematology, Oncology, Palliative Care, Heilbronn Hospital, Heilbronn, Germany., Department of Urology, Hospital University of Tübingen, Tübingen, Germany., Department of Urology, University Hospital Marburg and Philipps University Marburg, Marburg, Germany., Department of Urology and Urological Surgery, University Medical Centre Mannheim, Mannheim, Germany., Department Hematology, Hemostaseology, Oncology and Stem Cell Transplantation, Medical University Hannover, Hannover, Germany., Department of Urology, Diakonie-Klinikum Stuttgart, Stuttgart, Germany., Urology Department, Jena University Hospital, Jena, Germany., Department of Oncology, Red Cross Hospital, Munich, Germany., Department of Urology, Bundeswehrkrankenhaus Koblenz, Koblenz, Germany., Institute for Urologic Oncology, West-German Cancer Center Essen, University Hospital Essen and German Cancer Consortium (DKTK), Essen, Germany.