학술논문
Use of concomitant proton pump inhibitors, statins or metformin in patients treated with pembrolizumab for metastatic urothelial carcinoma: data from the ARON-2 retrospective study
Document Type
Original Paper
Author
Fiala, Ondřej; Buti, Sebastiano; Takeshita, Hideki; Okada, Yohei; Massari, Francesco; Palacios, Georgia Anguera; Dionese, Michele; Scagliarini, Sarah; Büttner, Thomas; Fornarini, Giuseppe; Myint, Zin W.; Galli, Luca; Souza, Vinicius Carrera; Pichler, Renate; De Giorgi, Ugo; Quiroga, María Natalia Gandur; Gilbert, Danielle; Popovic, Lazar; Grande, Enrique; Mammone, Giulia; Berardi, Rossana; Crabb, Simon J.; 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; Vau, Nuno; Giannatempo, Patrizia; Barillas, Allan; Monteiro, Fernando Sabino Marques; Dauster, Breno; Cattrini, Carlo; Nogueira, Lucas; de Carvalho Fernandes, Roni; Seront, Emmanuel; Aceituno, Luís Garcia; Grillone, Francesco; Cutuli, Hernan Javier; Fernandez, Mauricio; Bassanelli, Maria; Roviello, Giandomenico; Abahssain, Halima; Procopio, Giuseppe; Milella, Michele; Kopecky, Jindrich; Martignetti, Angelo; Messina, Carlo; Caitano, Manuel; Inman, Eva; Kanesvaran, Ravindran; Herchenhorn, Daniel; Santini, Daniele; Manneh, Ray; Bisonni, Renato; Zakopoulou, Roubini; 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; Sorgentoni, Giulia; Battelli, Nicola; Porta, Camillo; Bellmunt, Joaquim; Santoni, Matteo
Source
Cancer Immunology, Immunotherapy. 72(11):3665-3682
Subject
Language
English
ISSN
0340-7004
1432-0851
1432-0851
Abstract
Background: Concomitant medications may potentially affect the outcome of cancer patients. In this sub-analysis of the ARON-2 real-world study (NCT05290038), we aimed to assess the impact of concomitant use of proton pump inhibitors (PPI), statins, or metformin on outcome of patients with metastatic urothelial cancer (mUC) receiving second-line pembrolizumab.Methods: We collected data from the hospital medical records of patients with mUC treated with pembrolizumab as second-line therapy at 87 institutions from 22 countries. Patients were assessed for overall survival (OS), progression-free survival (PFS), and overall response rate. We carried out a survival analysis by a Cox regression model.Results: A total of 802 patients were eligible for this retrospective study; the median follow-up time was 15.3 months. PPI users compared to non-users showed inferior PFS (4.5 vs. 7.2 months, p = 0.002) and OS (8.7 vs. 14.1 months, p < 0.001). Concomitant PPI use remained a significant predictor of PFS and OS after multivariate Cox analysis. The use of statins or metformin was not associated with response or survival.Conclusions: Our study results suggest a significant prognostic impact of concomitant PPI use in mUC patients receiving pembrolizumab in the real-world context. The mechanism of this interaction warrants further elucidation.