BACKGROUND: Enfortumab vedotin (EV) has been approved for the treatment of patients with locally advanced/metastatic urothelial carcinoma (la/mUC) who previously received platinum-based chemotherapy followed by immune checkpoint inhibitors. However, the pivotal clinical trials did not include patients previously treated with avelumab maintenance therapy. OBJECTIVE: The aim of the present retrospective analysis was to assess the effectiveness of EV following avelumab in patients with mUC enrolled in the ARON-2EV study. PATIENTS AND METHODS: The study included 182 patients with mUC treated with EV following avelumab maintenance. The primary objective was to assess clinical outcomes, including progression-free survival (PFS), overall survival (OS), overall response rate (ORR), and duration of response (DoR). Statistical analysis involved Fisher exact test, Kaplan-Meier method, log-rank test, and univariate/multivariate Cox proportional hazard regression models. RESULTS: Median OS and PFS were 12.7 (95% CI 10.2-14.1) and 7.9 (95% CI 6.4-9.9) months, respectively. Complete response (CR) was achieved in 5% and partial response (PR) in 34% of patients, with an ORR of 39%. The DoR in patients who achieved CR/PR was 10.9 months (95% CI 8.1-11.4). The incidence of grade ≥ 3 peripheral neuropathy and skin rash was 9%, followed by 8% of grade ≥ 3 diarrhea and 4% of grade ≥ 3 hyperglycemia. CONCLUSIONS: The results of our large international retrospective study confirm the effectiveness of EV and endorse its use in the population of patients with mUC treated with EV following the frontline platinum-based chemotherapy and subsequent maintenance treatment with avelumab.

2nd Propaedeutic Department of Internal Medicine School of Medicine ATTIKON University Hospital National and Kapodistrian University of Athens Athens Greece

Biomedical Center Faculty of Medicine in Pilsen Charles University Pilsen Czech Republic

Centro Paulista de Oncologia Oncoclínicas São Paulo SP Brazil

Clinical Oncology Genitourinary Oncology Unit Alexander Fleming Institute Buenos Aires Argentina

Department of Health Sciences Section of Clinical Pharmacology and Oncology University of Florence Viale Pieraccini 6 Florence Italy

Department of Hemato Oncology Instituto Nacional de Ciencias Medicas y Nutricion Salvador Zubiran Mexico City Mexico

Department of Internal Medicine and Medical Specialties University of Genoa Genoa Italy

Department of Medical and Surgical Sciences University of Bologna Bologna Italy

Department of Medical Oncology Bakirköy Dr SadiKonuk Training and Research Hospital Tevfik Bakirkoy Istanbul Turkey

Department of Medical Oncology Cliniques Universitaires Saint Luc Brussels Belgium

Department of Medical Oncology Faculty of Medicine Ankara University Ankara Turkey

Department of Medical Oncology Hospital Ramón y Cajal Madrid Spain

Department of Medical Oncology IRCCS Istituto Romagnolo per lo Studio dei Tumori Dino Amadori Meldola Italy

Department of Medical Oncology MD Anderson Cancer Center Madrid Madrid Spain

Department of Medical Oncology San Camillo Forlanini Hospital Rome Italy

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 Czech Republic

Department of Oncology and Radiotherapeutics Faculty of Medicine University Hospital in Pilsen Charles University alej Svobody 80 30460 Pilsen Czech Republic

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

Department of Uro Oncology Maria Sklodowska Curie National Research Institute of Oncology Warsaw Warsaw Poland

Department of Urology Medical University of Innsbruck Innsbruck Austria

Department of Urology Saitama Medical Center Saitama Medical University Saitama Japan

Dipartimento di Oncologia Ospedale San Lazzaro Azienda sanitaria locale CN2 Alba Cuneo Italy

Division of Cancer Prevention and Genetics IEO European Institute of Oncology IRCCS 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 Singapore

Escuela de Medicina Universidad Panamericana Mexico City Mexico

Faculty of Medicine Masaryk University Brno Czech Republic

Harvard Medical School Boston MA USA

Hospital Israelita Albert Einstein São Paulo SP Brazil

Hospital Sírio Libanês Brasília DF Brazil

Interdisciplinary Department of Medicina Division of Medical Oncology University of Bari Aldo Moro A O U Consorziale Policlinico di Bari Bari Italy

IRCCS Ospedale Policlinico San Martino Genoa Italy

Lank Center for Genitourinary Oncology Dana Farber Cancer Institute Boston MA USA

Latin American Cooperative Oncology Group LACOG Porto Alegre Brazil

Masaryk Memorial Cancer Institute Brno Czech Republic

Medical Oncology 1 IRCCS Regina Elena National Cancer Institute Rome Italy

Medical Oncology 1 Unit Department of Oncology Istituto Oncologico Veneto IOV IRCCS 35128 Padova Italy

Medical Oncology Department Fondazione IRCCS Istituto Nazionale dei Tumori Via Giacomo Venezian 1 Milan Italy

Medical Oncology IRCCS Azienda Ospedaliero Universitaria di Bologna Bologna Italy

Medical Oncology Ospedale Santa Corona Pietra Ligure Italy

Medical Oncology Unit 2 Azienda Ospedaliera Universitaria Pisana Pisa Italy

Medical Oncology Unit Azienda Ospedaliera Universitaria Consorziale Policlinico di Bari Bari Italy

Medical Oncology Unit Macerata Hospital Macerata Italy

Medical Oncology Unit Ospedale San Paolo Savona Italy

Medical Oncology Unit University Hospital of Parma Parma Italy

Oncologia Dip Scienze e Biotecnologie Medico chirurgiche Policlinico Umberto 1 Rome Italy

Oncology Unit A R N A S Civico Palermo Italy

Oncology Unit Department of Oncology and Hematology Santa Maria delle Croci Hospital AUSL Romagna Ravenna Italy

Oncology Unit S Maria Delle Grazie Hospital ASL NA2 NORD Pozzuoli Naples Italy

Samsung Medical Center Sungkyunkwan University School of Medicine Seoul Korea

Servicio de Oncología Hospital Universitario La Paz Madrid Spain

Taussig Cancer Institute Cleveland Clinic Cleveland OH USA

U O Oncologia Ospedale di Civitanova Marche Civitanova Marche Italy

Unità Operativa di Oncologia Presidio Pugliese Ciaccio Azienda Ospedaliera Universitaria Renato Dulbecco Catanzaro Italy

UOC Oncologia Territoriale Ausl Latina Aprilia Italy

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