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.
Global real-world experiences with pembrolizumab in advanced urothelial carcinoma after platinum-based chemotherapy: the ARON-2 study / 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. - In: CANCER IMMUNOLOGY, IMMUNOTHERAPY. - ISSN 1432-0851. - ELETTRONICO. - 73:6(2024), pp. 1-13. [10.1007/s00262-024-03682-w]
Global real-world experiences with pembrolizumab in advanced urothelial carcinoma after platinum-based chemotherapy: the ARON-2 study
Massari, Francesco
Primo
;Marchetti, Andrea;Rosellini, Matteo;
2024
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.I documenti in IRIS sono protetti da copyright e tutti i diritti sono riservati, salvo diversa indicazione.
