Real‐Life Impact of Enfortumab Vedotin or Chemotherapy in the Sequential Treatment of Advanced Urothelial Carcinoma: The ARON‐2 Retrospective Experience

ABSTRACT Background Recently, a plethora of novel systemic agents have been incorporated into the therapeutic armamentarium of advanced urothelial carcinoma (aUC). The antibody–drug conjugate (ADC), enfortumab vedotin (EV), has demonstrated relevant clinical benefit in patients with aUC refractory t...

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Main Authors: Mimma Rizzo, Franco Morelli, Yüksel Ürün, Sebastiano Buti, Se Hoon Park, Maria T. Bourlon, Enrique Grande, Francesco Massari, Johannes Landmesser, Alexandr Poprach, Hideki Takeshita, Giandomenico Roviello, Zin W. Myint, Lazar Popovic, Andrey Soares, Halima Abahssain, Patrizia Giannatempo, Javier Molina‐Cerrillo, Lorena Incorvaia, Samer Salah, Annalisa Zeppellini, Fernando Sabino Marques Monteiro, Camillo Porta, Shilpa Gupta, Matteo Santoni
Format: Article
Language:English
Published: Wiley 2025-02-01
Series:Cancer Medicine
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Online Access:https://doi.org/10.1002/cam4.70479
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author Mimma Rizzo
Franco Morelli
Yüksel Ürün
Sebastiano Buti
Se Hoon Park
Maria T. Bourlon
Enrique Grande
Francesco Massari
Johannes Landmesser
Alexandr Poprach
Hideki Takeshita
Giandomenico Roviello
Zin W. Myint
Lazar Popovic
Andrey Soares
Halima Abahssain
Patrizia Giannatempo
Javier Molina‐Cerrillo
Lorena Incorvaia
Samer Salah
Annalisa Zeppellini
Fernando Sabino Marques Monteiro
Camillo Porta
Shilpa Gupta
Matteo Santoni
author_facet Mimma Rizzo
Franco Morelli
Yüksel Ürün
Sebastiano Buti
Se Hoon Park
Maria T. Bourlon
Enrique Grande
Francesco Massari
Johannes Landmesser
Alexandr Poprach
Hideki Takeshita
Giandomenico Roviello
Zin W. Myint
Lazar Popovic
Andrey Soares
Halima Abahssain
Patrizia Giannatempo
Javier Molina‐Cerrillo
Lorena Incorvaia
Samer Salah
Annalisa Zeppellini
Fernando Sabino Marques Monteiro
Camillo Porta
Shilpa Gupta
Matteo Santoni
author_sort Mimma Rizzo
collection DOAJ
description ABSTRACT Background Recently, a plethora of novel systemic agents have been incorporated into the therapeutic armamentarium of advanced urothelial carcinoma (aUC). The antibody–drug conjugate (ADC), enfortumab vedotin (EV), has demonstrated relevant clinical benefit in patients with aUC refractory to platinum and immune‐checkpoint inhibitor (ICI) therapy. Our study provides a retrospective, international, real‐world analysis comparing the effectiveness of EV to chemotherapy in this setting. Methods The data were extracted from the medical records of patients treated with EV or chemotherapy following pembrolizumab for recurrent or progressive aUC after platinum‐based chemotherapy. Patients were assessed for overall survival (OS), progression‐free survival (PFS), overall response rate (ORR) and duration of response (DoR). Results Our analysis included 247 patients treated with EV (88, 36%) or chemotherapy (159, 64%). Median OS was 9.1 months (95%CI 7.2–10.7) in the overall study population, 13.6 months (95%CI 10.0–31.0) in patients receiving EV and 6.8 months (95%CI 6.0–8.9) in patients receiving chemotherapy (p < 0.001). The OS benefit of EV was not affected by primary tumour site and histology, metastatic sites, type of first platinum‐based chemotherapy or response to pembrolizumab. In the EV cohort, the median PFS was significantly longer (8.8 months [95%CI 6.5–17.0] vs. 3.0 months [95%CI 2.6–3.7]) and the ORR was significantly higher (56% vs. 23%) than in the chemotherapy cohort. Conclusions The results of our international analysis of real‐world data confirm the effectiveness of EV in the sequential strategy of aUC patients who have received prior platinum‐based chemotherapy and anti‐PD‐1 pembrolizumab, regardless of commonly considered prognostic factors. Trial Registration: ClinicalTrials.gov identifier: NCT05290038
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spelling doaj-art-329cc815b0194bce9d4bc4fada26ea072025-08-20T02:27:39ZengWileyCancer Medicine2045-76342025-02-01144n/an/a10.1002/cam4.70479Real‐Life Impact of Enfortumab Vedotin or Chemotherapy in the Sequential Treatment of Advanced Urothelial Carcinoma: The ARON‐2 Retrospective ExperienceMimma Rizzo0Franco Morelli1Yüksel Ürün2Sebastiano Buti3Se Hoon Park4Maria T. Bourlon5Enrique Grande6Francesco Massari7Johannes Landmesser8Alexandr Poprach9Hideki Takeshita10Giandomenico Roviello11Zin W. Myint12Lazar Popovic13Andrey Soares14Halima Abahssain15Patrizia Giannatempo16Javier Molina‐Cerrillo17Lorena Incorvaia18Samer Salah19Annalisa Zeppellini20Fernando Sabino Marques Monteiro21Camillo Porta22Shilpa Gupta23Matteo Santoni24Medical Oncology Unit Azienda Ospedaliera Universitaria Consorziale Policlinico di Bari Bari ItalyMedical Oncology Unit IRCCS Casa Sollievo della Sofferenza Foggia ItalyDepartment of Medical Oncology, Faculty of Medicine Ankara University Ankara TurkeyDepartment of Medicine and Surgery University of Parma Parma ItalySamsung Medical Center Sungkyunkwan University School of Medicine Seoul KoreaDepartment of Hemato‐Oncology, Instituto Nacional de Ciencias Medicas y Nutricion Salvador Zubiran Universidad Panamericana Mexico City MexicoDepartment of Medical Oncology MD Anderson Cancer Center Madrid Madrid SpainDepartment of Medical and Surgical Sciences (DIMEC) University of Bologna Bologna ItalyKlinik für Urologie Universitätsklinikum Schleswig‐Holstein Campus Lübeck Lübeck GermanyDepartment of Comprehensive Cancer Care Masaryk Memorial Cancer Institute Brno Czech RepublicDepartment of Urology, Saitama Medical Center Saitama Medical University Saitama JapanDepartment of Health Sciences, Section of Clinical Pharmacology and Oncology University of Florence Florence ItalyDivision of Medical Oncology, Department of Internal Medicine, Markey Cancer Center University of Kentucky Lexington Kentucky USAFaculty of Medicine, Oncology Institute of Vojvodina University of Novi Sad Novi Sad SerbiaHospital Israelita Albert Einstein São Paulo BrazilMedicine and Pharmacy Faculty, National Institute of Oncology, Medical Oncology Unit Mohamed V University Rabat MoroccoMedical Oncology Department Fondazione IRCCS Istituto Nazionale dei Tumori Milan ItalyDepartment of Medical Oncology Hospital Ramón y Cajal Madrid SpainDepartment of Precision Medicine in Medical, Surgical and Critical Care (Me.Pre.C.C.), Section of Medical Oncology University of Palermo Palermo ItalyDepartment of Adult Medical Oncology King Fahad Specialist Hospital‐Dammam Dammam Saudi ArabiaNiguarda Cancer Center Grande Ospedale Metropolitano Niguarda Milan ItalyLatin American Cooperative Oncology Group–LACOG Porto Alegre BrazilChair of Oncology, Interdisciplinary Department of Medicine University of Bari “Aldo Moro” Bari ItalyTaussig Cancer Institute Cleveland Clinic Cleveland Ohio USAMedical Oncology Unit Macerata Hospital Macerata ItalyABSTRACT Background Recently, a plethora of novel systemic agents have been incorporated into the therapeutic armamentarium of advanced urothelial carcinoma (aUC). The antibody–drug conjugate (ADC), enfortumab vedotin (EV), has demonstrated relevant clinical benefit in patients with aUC refractory to platinum and immune‐checkpoint inhibitor (ICI) therapy. Our study provides a retrospective, international, real‐world analysis comparing the effectiveness of EV to chemotherapy in this setting. Methods The data were extracted from the medical records of patients treated with EV or chemotherapy following pembrolizumab for recurrent or progressive aUC after platinum‐based chemotherapy. Patients were assessed for overall survival (OS), progression‐free survival (PFS), overall response rate (ORR) and duration of response (DoR). Results Our analysis included 247 patients treated with EV (88, 36%) or chemotherapy (159, 64%). Median OS was 9.1 months (95%CI 7.2–10.7) in the overall study population, 13.6 months (95%CI 10.0–31.0) in patients receiving EV and 6.8 months (95%CI 6.0–8.9) in patients receiving chemotherapy (p < 0.001). The OS benefit of EV was not affected by primary tumour site and histology, metastatic sites, type of first platinum‐based chemotherapy or response to pembrolizumab. In the EV cohort, the median PFS was significantly longer (8.8 months [95%CI 6.5–17.0] vs. 3.0 months [95%CI 2.6–3.7]) and the ORR was significantly higher (56% vs. 23%) than in the chemotherapy cohort. Conclusions The results of our international analysis of real‐world data confirm the effectiveness of EV in the sequential strategy of aUC patients who have received prior platinum‐based chemotherapy and anti‐PD‐1 pembrolizumab, regardless of commonly considered prognostic factors. Trial Registration: ClinicalTrials.gov identifier: NCT05290038https://doi.org/10.1002/cam4.70479ARON‐2 studychemotherapyenfortumab vedotinNCT05290038pembrolizumabreal‐world data
spellingShingle Mimma Rizzo
Franco Morelli
Yüksel Ürün
Sebastiano Buti
Se Hoon Park
Maria T. Bourlon
Enrique Grande
Francesco Massari
Johannes Landmesser
Alexandr Poprach
Hideki Takeshita
Giandomenico Roviello
Zin W. Myint
Lazar Popovic
Andrey Soares
Halima Abahssain
Patrizia Giannatempo
Javier Molina‐Cerrillo
Lorena Incorvaia
Samer Salah
Annalisa Zeppellini
Fernando Sabino Marques Monteiro
Camillo Porta
Shilpa Gupta
Matteo Santoni
Real‐Life Impact of Enfortumab Vedotin or Chemotherapy in the Sequential Treatment of Advanced Urothelial Carcinoma: The ARON‐2 Retrospective Experience
Cancer Medicine
ARON‐2 study
chemotherapy
enfortumab vedotin
NCT05290038
pembrolizumab
real‐world data
title Real‐Life Impact of Enfortumab Vedotin or Chemotherapy in the Sequential Treatment of Advanced Urothelial Carcinoma: The ARON‐2 Retrospective Experience
title_full Real‐Life Impact of Enfortumab Vedotin or Chemotherapy in the Sequential Treatment of Advanced Urothelial Carcinoma: The ARON‐2 Retrospective Experience
title_fullStr Real‐Life Impact of Enfortumab Vedotin or Chemotherapy in the Sequential Treatment of Advanced Urothelial Carcinoma: The ARON‐2 Retrospective Experience
title_full_unstemmed Real‐Life Impact of Enfortumab Vedotin or Chemotherapy in the Sequential Treatment of Advanced Urothelial Carcinoma: The ARON‐2 Retrospective Experience
title_short Real‐Life Impact of Enfortumab Vedotin or Chemotherapy in the Sequential Treatment of Advanced Urothelial Carcinoma: The ARON‐2 Retrospective Experience
title_sort real life impact of enfortumab vedotin or chemotherapy in the sequential treatment of advanced urothelial carcinoma the aron 2 retrospective experience
topic ARON‐2 study
chemotherapy
enfortumab vedotin
NCT05290038
pembrolizumab
real‐world data
url https://doi.org/10.1002/cam4.70479
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