Global real-world experiences with pembrolizumab in advanced urothelial carcinoma after platinum-based chemotherapy: the ARON-2 study

Author:

Massari Francesco,Santoni Matteo,Takeshita Hideki,Okada Yohei,Tapia Jose Carlos,Basso Umberto,Maruzzo Marco,Scagliarini Sarah,Büttner Thomas,Fornarini Giuseppe,Myint Zin W.,Galli Luca,Souza Vinicius Carrera,Pichler Renate,De Giorgi Ugo,Gandur Nathalia,Lam Elaine T.,Gilbert Danielle,Popovic Lazar,Grande Enrique,Mammone Giulia,Berardi Rossana,Crabb Simon J.,Kemp Robert,Molina-Cerrillo Javier,Freitas Marcelo,Luz Murilo,Iacovelli Roberto,Calabrò Fabio,Tural Deniz,Atzori Francesco,Küronya Zsófia,Chiari Rita,Campos Saul,Caffo Orazio,Fay André P.,Kucharz Jakub,Zucali Paolo Andrea,Rinck José Augusto,Zeppellini Annalisa,Bastos Diogo Assed,Aurilio Gaetano,Mota Augusto,Trindade Karine,Ortega Cinzia,Sade Juan Pablo,Rizzo Mimma,Fiala Ondřej,Vau Nuno,Giannatempo Patrizia,Barillas Allan,Monteiro Fernando Sabino M.,Dauster Breno,Mennitto Alessia,Nogueira Lucas,de Carvalho Fernandes Roni,Seront Emmanuel,Aceituno Luís Garcia,Grillone Francesco,Cutuli Hernan Javier,Fernandez Mauricio,Bassanelli Maria,Kopp Ray Manneh,Roviello Giandomenico,Abahssain Halima,Procopio Giuseppe,Milella Michele,Kopecky Jindrich,Martignetti Angelo,Messina Carlo,Caitano Manuel,Inman Eva,Kanesvaran Ravindran,Herchhorn Daniel,Santini Daniele,Bamias Aristotelis,Bisonni Renato,Mosca Alessandra,Morelli Franco,Maluf Fernando,Soares Andrey,Nunes Fernando,Pinto Alvaro,Zgura Anca,Incorvaia Lorena,Ansari Jawaher,Zabalza Ignacio Ortego,Landmesser Johannes,Rizzo Alessandro,Mollica Veronica,Marchetti Andrea,Rosellini Matteo,Sorgentoni Giulia,Battelli Nicola,Buti Sebastiano,Porta Camillo,Bellmunt Joaquim

Abstract

Abstract Background 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. Patients and Methods 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. Results 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). Conclusions 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.

Funder

Alma Mater Studiorum - Università di Bologna

Publisher

Springer Science and Business Media LLC

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