BACKGROUND AND OBJECTIVE: Enfortumab vedotin (EV) has demonstrated efficacy in metastatic urothelial carcinoma (mUC) following treatment with platinum-based chemotherapy (PBC) and PD-1/PD-L1 inhibitors, including pembrolizumab (PEM). Our aim was to assess real-world clinical outcomes of EV in patients with mUC previously treated with PBC followed by pembrolizumab (PBC/PEM). METHODS: ARON-2EV is an international, multicenter, retrospective study examining the real-world use of EV in patients with mUC. This analysis included 401 patients with mUC treated with EV following PBC/PEM. Primary endpoints were overall survival (OS), time on treatment (ToT), and the overall response rate (ORR). Secondary objectives included evaluation of clinical factors associated with outcomes and exploration of the impact of prior PEM outcomes. Statistical methods included Kaplan-Meier estimates, log-rank tests, Fisher's exact and χ2 tests, Pearson's correlation coefficients, and Cox analyses. KEY FINDINGS AND LIMITATIONS: Median OS was 12.3 mo (95% confidence interval [CI] 9.9-14.3), median ToT was 10.4 mo (95% CI 9.0-12.2), and the ORR was 45%. Prior response to PEM was significantly correlated with subsequent outcomes on EV. In the group who experienced progressive disease (PD) on prior PEM, the ORR was 35%. Major limitations are related to the retrospective study design. CONCLUSIONS: EV has consistent real-world efficacy in patients with mUC following sequential treatment with PBC/PEM. These results support the utility of EV in diverse clinical scenarios and suggest an association between prior PEM outcomes and subsequent EV efficacy. PATIENT SUMMARY: The ARON-2EV project is collecting real-world data for patients with metastatic cancer of the urinary tract who are being treated with a drug called enfortumab vedotin (EV) in multiple centers worldwide. Our results show that EV has consistent efficacy in these patients after previous treatment with platinum-based chemotherapy followed by pembrolizumab. The results also suggest an association between a patient's response to pembrolizumab and their subsequent response to EV.

Barts Cancer Centre St Bartholomew's Hospital Barts Health NHS Trust London UK

Biomedical Center Faculty of Medicine Charles University Pilsen Czechia

Clínica Assistência Multidisciplinar em Oncologia Salvador Brazil

Dana Farber Cancer Institute Harvard Medical School Boston MA USA

Department of Medical and Surgical Sciences University of Bologna Bologna Italy

Department of Medical Oncology MD Anderson Cancer Center Madrid Madrid Spain

Department of Medicine and Surgery Federico 2 University Naples Italy

Department of Medicine and Surgery University of Parma Parma Italy

Department of Oncology 2nd Faculty of Medicine Charles University and University Hospital Motol Prague Czechia

Department of Oncology and Radiotherapeutics Faculty of Medicine and University Hospital Pilsen Charles University Pilsen Czechia

Department of Oncology Palacký University Medical School and Teaching Hospital Olomouc Czechia

Department of Oncology Portsmouth Hospitals University NHS Trust Portsmouth UK

Department of Oncology University Hospital Hradec Králové Hradec Králové Czechia

Department of Precision Medicine in Medical Surgical and Critical Care Section of Medical Oncology University of Palermo Palermo Italy

Department of Urology Kindai University Osaka Japan

Department of Urology Saitama Medical Center Saitama Medical University Kawagoe Saitama Japan

Department of Urology University Hospital Bonn Bonn Germany

Dipartimento di Oncologia Medica Fondazione IRCCS Istituto Nazionale dei Tumori Milan Italy

Division of Medical Oncology Department of Internal Medicine Markey Cancer Center University of Kentucky Lexington KY USA

Division of Medical Oncology National Cancer Centre Singapore Singapore

Division of Oncology S Corona Hospital Pietra Ligure Italy

Faculty of Medicine Masaryk University Brno Czechia

Latin American Cooperative Oncology Group Porto Alegre Brazil

Masaryk Memorial Cancer Institute Brno Czechia

Medical Oncology Department CHU Insular Materno Infantil Las Palmas Spain

Medical Oncology IRCCS Azienda Ospedaliero Universitaria di Bologna Bologna Italy

Medical Oncology Unit Livorno Hospital Azienda Toscana Nord Ovest Livorno Italy

Medical Oncology Unit Macerata Hospital Macerata Italy

Medical Oncology Unit University Hospital of Parma Parma Italy

Oncology and Hematology Department Hospital Sírio Libanês Brasília Brazil

Oncology Operative Unit Santa Maria delle Grazie Hospital Pozzuoli Italy

Oncology Unit Hospital Israelita Albert Einstein São Paulo Brazil

Royal Marsden NHS Foundation Trust London UK

School of Pharmacy and Biomedical Sciences University of Portsmouth Portsmouth UK

SOC Oncologia PO Pugliese Ciaccio Azienda Ospedaliera Universitaria Renato Dulbecco Catanzaro Italy

Taussig Cancer Institute Cleveland Clinic Cleveland OH USA

Unit of Medical Oncology and Biomolecular Therapy Department of Medical and Surgical Sciences University of Foggia Policlinico Riuniti Foggia Italy

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