Immune checkpoint inhibitors have changed previous treatment paradigm of advanced urothelial carcinoma (UC). The ARON-2 study (NCT05290038) aimed to assess the real-world effectiveness of pembrolizumab in patients recurred or progressed after platinum-based chemotherapy.
Medical records of patients with documented metastatic UC treated by pembrolizumab as second-line therapy were retrospectively collected from 88 institutions in 23 countries. Patients were assessed for overall survival (OS), progression-free survival (PFS) and overall response rate (ORR). Cox proportional hazards models were adopted to explore the presence of prognostic factors.
In total, 836 patients were included: 544 patients (65%) received pembrolizumab after progression to first-line platinum-based chemotherapy in the metastatic setting (cohort A) and 292 (35%) after recurring within < 12 months since the completion of adjuvant or neoadjuvant chemotherapy (cohort B). The median follow-up time was 15.3 months. The median OS and the ORR were 10.5 months and 31% in the overall study population, 9.1 months and 29% in cohort A and 14.6 months and 37% in cohort B. At multivariate analysis, ECOG-PS ≥ 2, bone metastases, liver metastases and pembrolizumab setting (cohort A vs B) proved to be significantly associated with worst OS and PFS. Stratified by the presence of 0, 1-2 or 3-4 prognostic factors, the median OS was 29.4, 12.5 and 4.1 months (p < 0.001), while the median PFS was 12.2, 6.4 and 2.8 months, respectively (p < 0.001).
Our study confirms that pembrolizumab is effective in the advanced UC real-world context, showing outcome differences between patients recurred or progressed after platinum-based chemotherapy.
Cancer immunology, immunotherapy : CII. 2024 Apr 18*** epublish ***
Francesco Massari, Matteo Santoni, Hideki Takeshita, Yohei Okada, Jose Carlos Tapia, Umberto Basso, Marco Maruzzo, Sarah Scagliarini, Thomas Büttner, Giuseppe Fornarini, Zin W Myint, Luca Galli, Vinicius Carrera Souza, Renate Pichler, Ugo De Giorgi, Nathalia Gandur, Elaine T Lam, Danielle Gilbert, Lazar Popovic, Enrique Grande, Giulia Mammone, Rossana Berardi, Simon J Crabb, Robert Kemp, Javier Molina-Cerrillo, Marcelo Freitas, Murilo Luz, Roberto Iacovelli, Fabio Calabrò, Deniz Tural, Francesco Atzori, Zsófia Küronya, Rita Chiari, Saul Campos, Orazio Caffo, André P Fay, Jakub Kucharz, Paolo Andrea Zucali, José Augusto Rinck, Annalisa Zeppellini, Diogo Assed Bastos, Gaetano Aurilio, Augusto Mota, Karine Trindade, Cinzia Ortega, Juan Pablo Sade, Mimma Rizzo, Ondřej Fiala, Nuno Vau, Patrizia Giannatempo, Allan Barillas, Fernando Sabino M Monteiro, Breno Dauster, Alessia Mennitto, Lucas Nogueira, Roni de Carvalho Fernandes, Emmanuel Seront, Luís Garcia Aceituno, Francesco Grillone, Hernan Javier Cutuli, Mauricio Fernandez, Maria Bassanelli, Ray Manneh Kopp, Giandomenico Roviello, Halima Abahssain, Giuseppe Procopio, Michele Milella, Jindrich Kopecky, Angelo Martignetti, Carlo Messina, Manuel Caitano, Eva Inman, Ravindran Kanesvaran, Daniel Herchhorn, Daniele Santini, Aristotelis Bamias, Renato Bisonni, Alessandra Mosca, Franco Morelli, Fernando Maluf, Andrey Soares, Fernando Nunes, Alvaro Pinto, Anca Zgura, Lorena Incorvaia, Jawaher Ansari, Ignacio Ortego Zabalza, Johannes Landmesser, Alessandro Rizzo, Veronica Mollica, Andrea Marchetti, Matteo Rosellini, Giulia Sorgentoni, Nicola Battelli, Sebastiano Buti, Camillo Porta, Joaquim Bellmunt
Medical Oncology, IRCCS Azienda Ospedaliero-Universitaria di Bologna, Bologna, Italy. ., Oncology Unit, Macerata Hospital, via Santa Lucia 2, 62100, Macerata, Italy., Department of Urology, Saitama Medical Center, Saitama Medical University, Saitama, Japan., Department of Medical Oncology, Institut d'Investigació Biomèdica Sant Pau, Hospital de la Santa Creu i Sant Pau, Barcelona, Spain., Medical Oncology 1 Unit, Department of Oncology, Istituto Oncologico Veneto IOV IRCCS, 35128, Padova, Italy., UOC di Oncologia, Azienda Ospedaliera di Rilievo Nazionale Cardarelli di Napoli, Naples, Italy., Department of Urology, University Hospital Bonn (UKB), 53127, Bonn, Germany., IRCCS Ospedale Policlinico San Martino, Genoa, Italy., Markey Cancer Center, University of Kentucky, Lexington, KY, 40536-0293, USA., Oncology Unit 2, University Hospital of Pisa, 56126, Pisa, Italy., Hospital São Rafael Oncologia D'Or, Salvador, BA, Brazil., Department of Urology, Medical University of Innsbruck, Anichstrasse 35, 6020, Innsbruck, Austria., Department of Medical Oncology, IRCCS Istituto Romagnolo per lo Studio dei Tumori (IRST) "Dino Amadori", Meldola, Italy., Latin American Cooperative Oncology Group - LACOG, Porto Alegre, Brazil., University of Colorado Anschutz Medical Campus, Aurora, CO, USA., Oncology Institute of Vojvodina, Faculty of Medicine, University Novi Sad, Novi Sad, Serbia., Department of Medical Oncology, MD Anderson Cancer Center Madrid, Madrid, Spain., Department of Radiological, Oncological and Anatomo-Pathological Science, "Sapienza" University of Rome, Viale Regina Elena 324, 00185, Rome, Italy., Department of Medical Oncology, Università Politecnica Delle Marche, AOU Ospedali Riuniti Delle Marche, Ancona, Italy., Southampton Experimental Cancer Medicine Centre, University of Southampton, Southampton, UK., Department of Medical Oncology, Hospital Ramón y Cajal, Madrid, Spain., Oncologia Medica, Fondazione Policlinico Universitario Agostino Gemelli IRCCS, Rome, Italy., Department of Oncology, San Camillo Forlanini Hospital, Rome, Italy., Department of Medical Oncology, Bakirköy Dr. SadiKonuk Training and Research Hospital, Tevfik Saglam St. No: 11, Zuhuratbaba District, Bakirkoy, Istanbul, Turkey., Unità di Oncologia Medica, Azienda Ospedaliero Universitaria di Cagliari, Cagliari, Italy., Department of Genitourinary Medical Oncology and Clinical Pharmacology, National Institute of Oncology, Budapest, Hungary., UOC Oncologia, Azienda Ospedaliera Ospedali Riuniti Marche Nord, Fano, Italy., Medical Oncology Unit, Santa Chiara Hospital, Trento, Italy., Department of Uro-Oncology, Maria Sklodowska-Curie National Research Institute of Oncology Warsaw, Warsaw, Poland., Department of Oncology, IRCCS Humanitas Research Hospital, Rozzano - Milan, Italy., Niguarda Cancer Center, Grande Ospedale Metropolitano Niguarda, Milan, Italy., Division of Cancer Prevention and Genetics, IEO European Institute of Oncology IRCCS, Milan, Italy., ASLCN2 Alba-Bra, Ospedale Michele E Pietro Ferrero, Verduno, CN, Italy., Instituto Alexander Fleming, Buenos Aires, CABA, Argentina., Division of Medical Oncology, A.O.U. Consorziale Policlinico Di Bari, Piazza G. Cesare 11, 70124, Bari, Italy., Department of Oncology and Radiotherapeutics, Faculty of Medicine, University Hospital in Pilsen, Charles University, Pilsen, Czech Republic., Urologic Oncology, Champalimaud Clinical Center, 1400-038, Lisbon, Portugal., Dipartimento di Oncologia Medica, Fondazione IRCCS Istituto Nazionale Dei Tumori, Milan, Italy., Department of Medical Oncology, "Maggiore Della Carità" University Hospital, 28100, Novara, Italy., Department of Medical Oncology, Centre Hospitalier de Jolimont, Haine Saint Paul, Belgium., UO Oncologia Azienda Ospedaliera Universitaria Renato Dulbecco PO Pugliese Ciaccio Catanzaro, Catanzaro, Italy., Medical Oncology 1-IRCCS Regina Elena National Cancer Institute, Rome, Italy., Clinical Oncology, Sociedad de Oncología y Hematología del Cesar, Valledupar, Colombia., Department of Health Sciences, Section of Clinical Pharmacology and Oncology, University of Florence, Viale Pieraccini 6, 50139, Florence, Italy., Medicine and Pharmacy Faculty, National Institute of Oncology, Medical Oncology Unit, Mohamed V University, Rabat, Morocco., Section of Oncology, Department of Medicine, University of Verona School of Medicine and Verona University Hospital Trust, Verona, Italy., Department of Clinical Oncology and Radiotherapy, University Hospital Hradec Kralove, Hradec Kralove, Czech Republic., Dipartimento Oncologico USL Sud-Est Toscana-Area Senese, Località Campostaggia S.N.C, 53036, Poggibonsi, Italy., Oncology Unit, A.R.N.A.S. Civico, Palermo, Italy., National Cancer Centre Singapore, Singapore, Singapore., Department of Radiological, Oncological and Pathological Sciences, Policlinico Umberto I, University of Rome, SapienzaRome, Italy., 2nd Propaedeutic Department of Internal Medicine, ATTIKON University Hospital, School of Medicine, National and Kapodistrian University of Athens, Athens, Greece., UOC Oncologia Medica, Ospedale A. Murri, Fermo, Italy., Oncology, Candiolo Cancer Institute, IRCCS-FPO, 10060, Turin, Italy., Medical Oncology Unit, Gemelli Molise Hospital, Università Cattolica del Sacro Cuore, Campobasso, Italy., Medical Oncology Department, La Paz University Hospital, Madrid, Spain., Department of Oncology-Radiotherapy, Prof. Dr. Alexandru Trestioreanu Institute of Oncology, Carol Davila; University of Medicine and Pharmacy, Bucharest, Romania., Department of Precision Medicine in Medical, Surgical and Critical Care (Me.Pre.C.C.), Section of Medical Oncology, University of Palermo, Via del Vespro 129, 90127, Palermo, Italy., Medical Oncology, Tawam Hospital, Al Ain, United Arab Emirates., Klinik für Urologie, Ratzeburger Allee 160, 23538, Lübeck, Germany., Struttura Semplice Dipartimentale di Oncologia Medica per la Presa in Carico Globale del Paziente Oncologico "Don Tonino Bello", I.R.C.C.S. Istituto Tumori "Giovanni Paolo II", Viale Orazio Flacco 65, 70124, Bari, Italy., Medical Oncology, IRCCS Azienda Ospedaliero-Universitaria di Bologna, Bologna, Italy., Medical Oncology Unit, Department of Medicine and Surgery, University Hospital of Parma, University of Parma, Parma, Italy., Chair of Oncology, Interdisciplinary Department of Medicine, University of Bari "Aldo Moro", Bari, Italy., Dana Farber Cancer Institute, Harvard Medical School, Boston, MA, USA.