Global real-world experiences with pembrolizumab in advanced urothelial carcinoma after platinum-based chemotherapy: the ARON-2 study
Francesco Massari, Matteo Santoni, Hideki Takeshita, Y. Okada, José Carlos Tapia, Umberto Basso, Marco Maruzzo, Sarah Scagliarini, Thomas Büttner, Giuseppe Fornarini, Zin Myint, Luca Galli, Vinícius Carrera Souza, Renate Pichler, Ugo De Giorgi, Nathalia Gandur, Elaine T. Lam, Danielle Gilbert, Lazar Popović, Enrique Grande, Giulia Mammone, Rossana Berardi, Simon J. Crabb, ROBERT COLEMAN KEMP, Javier Molina‐Cerrillo, Marcelo Freitas, Murilo Luz, Roberto Iacovelli, Fabio Calabrò, Deniz Tural, Francesco Atzori, Zsófia Kürönya, Rita Chiari, Saúl Campos-Gómez, Orazio Caffo, André P. Fay, Jakub Kucharz, Paolo Andrea Zucali, José Augusto Rinck, Annalisa Zeppellini, Diogo Assed Bastos, Gaetano Aurilio, Augusto Mota, Karine Martins da Trindade, Cinzia Ortega, Juan Pablo Sade, Mimma Rizzo, Ondřej Fiala, Nuno Vau, Patrizia Giannatempo, Allan Barillas, Fernando Sabino Marques Monteiro, Breno Dauster, Alessia Mennitto, Lucas Nogueira, Roni de Carvalho Fernandes, Emmanuel Seront, Luis García Aceituno, Francesco Grillone, Hernan Javier Cutuli, Mauricio Fernández, Maria Bassanelli, Ray Manneh Kopp, Giandomenico Roviello, Halima Abahssain, Giuseppe Procopio, Michèle Milella, Jindřich Kopecký, Angelo Martignetti, Carlo Messina, Manuel Caitano, Eva Inman, Ravindran Kanesvaran, Daniel Herchhorn, Daniele Santini, Aristotelis Bamias, Renato Bisonni, Alessandra Mosca, Franco Morelli, Fernando Cotait Maluf, Andrey Soares, Fernando Furlan Nunes, Álvaro Pinto, Anca Zgură, 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
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.