Treatment options for patients with urothelial cancer (UC) refractory to platinum and immunotherapy are limited and survival is short. Enfortumab vedotin (EV) is a monoclonal anti-NECTIN4 antibody conjugated to monomethyl auristatin. It was recently approved because of superior survival in comparison to standard-of-care (SOC) chemotherapy. Real-world patients, however, often have worse characteristics than patients included in clinical trials.
To analyze the efficacy and safety of EV in a cohort of real-world patients.
Retrospective data were collected from 23 hospitals and private practices for patients with metastatic and previously treated UC who received EV either when reimbursed by their insurance company before European Medicines Agency (EMA) approval, within a compassionate use program, or as SOC treatment after EMA approval. Imaging and therapy management were in accordance with local standards.
Adverse events (AEs) were reported according to Common Terminology Criteria for Adverse Events (CTCAE) version 5.0 criteria. Objective responses were evaluated according to Response Evaluation Criteria in Solid Tumors version 1.1. Progression-free survival (PFS) and overall survival (OS) were estimated using the Kaplan-Meier method.
The median age for the 125 eligible patients was 66 yr (range 31-89). The Eastern Cooperative Oncology Group performance status (ECOG PS) was 0-1 for 76.0%, 2-4 for 13.6%, and unknown for 10.4% of patients. EV was administered in the fourth or later line for 44.8% of patients. The overall response rate was 41.6% (partial response 39.2%, complete response 2.4%). Median OS was 10.0 months (mo) (95% confidence interval 7.20-12.80) and median PFS was 5.0 mo (95% confidence interval 4.34-5.67). For patients with ECOG PS of 0-1, median OS was 14 mo. Any-grade AEs were observed in 67.2% and CTCAE grade ≥3 AEs in 30.4%. The most common AEs were peripheral sensory neuropathy and skin toxicity. Three fatal events (pneumonia, pneumonitis) occurred. Limitations include the retrospective design and short follow-up.
Administration of EV for real-world patients was feasible with an acceptable toxicity profile. No new safety signals were reported. Antitumor activity in our cohort was comparable to data previously reported for trials. In summary, our results support the use of EV in patients with metastatic UC.
Enfortumab vedotin is a medication that improved the survival of patients with bladder cancer in comparison to standard chemotherapy in clinical trials. However, patients included in clinical trials are highly selected and results for toxicities and improvements in survival do not always transfer to the real-world setting. We analyzed data for 125 patients who were treated with enfortumab vedotin. Our results are comparable to the outcomes from clinical trials regarding the safety and efficacy of this treatment.
European urology open science. 2023 May 17*** epublish ***
Stefanie Zschäbitz, Nadine Biernath, Thomas Hilser, Alexander Höllein, Friedemann Zengerling, Jozefina Cascucelli, Pia Paffenholz, Daniel Seidl, Christoph Lutz, Katrin Schlack, Dorothea Kingreen, Niklas Klümper, Philipp Ivanyi, Gunhild von Amsberg, Hendrik Heers, Florian Roghmann, Robert L Tauber, Richard Cathomas, Luisa Hofer, Günter Niegisch, Melanie Klee, Roland Ehrenberg, Andreas Hassler, Boris A Hadaschik, Viktor Grünwald, Christopher Darr
Department of Medical Oncology, National Center for Tumor Diseases Heidelberg, University Hospital Heidelberg, Heidelberg, Germany., Department of Urology, Charité University Medicine Berlin, Berlin, Germany., Department of Internal Medicine, West German Tumor Center Essen, University Hospital Essen, Essen, Germany., Medical Department, Hematology and Oncology, Rotkreuzklinikum Munich Munich, Germany., Department of Urology, University Hospital Ulm, Ulm, Germany., Department of Urology, University Hospital Munich, Munich, Germany., Department of Urology, Uro-Oncology, and Robot-Assisted and Reconstructive Urologic Surgery, University of Cologne Faculty of Medicine and University Hospital Cologne, Cologne, Germany., Diakonie-Klinikum Stuttgart, Stuttgart, Germany., Hematology and Oncology Koblenz, Koblenz, Germany., Department of Urology, University Hospital Münster, Münster, Germany., Oncologic Practice Tiergarten, Berlin, Germany., Department of Urology, University Medical Center Bonn, Bonn, Germany., Department of Hematology, Oncology and Stem Cell Transplantation, Medical University Hannover, Hannover, Germany., Department of Oncology & Hematology, University Cancer Center Hamburg & Martini Clinic, University Medical Center Hamburg-Eppendorf, Hamburg, Germany., Department of Urology, University Hospital Marburg, Marburg, Germany., Department of Urology, University Hospital Bochum, Herne, Germany., Department of Urology, Klinikum Rechts der Isar, Technical University Munich, Munich, Germany., Department of Internal Medicine, Medical Oncology and Hematology, Kantonsspital Graubünden, Chur, Switzerland., Urologic Hospital München-Planegg, Munich, Germany., Department of Urology, University Hospital and Medical Faculty, Heinrich-Heine University Düsseldorf, Düsseldorf, Germany., Department of Urology, University Hospital Schleswig-Holstein, Lübeck, Germany., Onkologische Schwerpunktpraxis, Heidelberg, Germany., Center for Urological Oncology, Palliative Medicine and General and Operative Urology, Berlin, Germany., Department of Urology, University Hospital Essen, Essen, Germany.