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

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

doi:10.1007/s00262-024-03682-w

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

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

Research output: Contribution to journal › Article › peer-review

13 Scopus citations

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.

Original language	English
Article number	106
Journal	Cancer Immunology, Immunotherapy
Volume	73
Issue number	6
DOIs	https://doi.org/10.1007/s00262-024-03682-w
State	Published - Jun 2024

Bibliographical note

Publisher Copyright:
© The Author(s) 2024.

Funding

Open access funding provided by Alma Mater Studiorum - Università di Bologna within the CRUI-CARE Agreement. The authors declare that no funds, grants or other support were received during the preparation of this manuscript.

Funders
Alma Mater Studiorum -Universita' di Bologna
Università di Bologna

Keywords

ARON-2 study
Pembrolizumab
Real-world data
Survival
Tumor response
Urothelial cancer

ASJC Scopus subject areas

Immunology and Allergy
Immunology
Oncology
Cancer Research

UN SDGs

This output contributes to the following UN Sustainable Development Goals (SDGs)

Access to Document

10.1007/s00262-024-03682-w

Cite this

Massari, F., Santoni, M., Takeshita, H., Okada, Y., Tapia, J. C., Basso, U., Maruzzo, M., Scagliarini, S., Büttner, T., Fornarini, G., Myint, Z. W., Galli, L., Souza, V. C., Pichler, R., De Giorgi, U., Gandur, N., Lam, E. T., Gilbert, D., Popovic, L., ... Bellmunt, J. (2024). Global real-world experiences with pembrolizumab in advanced urothelial carcinoma after platinum-based chemotherapy: the ARON-2 study. Cancer Immunology, Immunotherapy, 73(6), Article 106. https://doi.org/10.1007/s00262-024-03682-w

@article{40f359d7eefd48d991eab88ddcea999f,

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

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.",

keywords = "ARON-2 study, Pembrolizumab, Real-world data, Survival, Tumor response, Urothelial cancer",

author = "Francesco Massari and Matteo Santoni and Hideki Takeshita and Yohei Okada and Tapia, \{Jose Carlos\} and Umberto Basso and Marco Maruzzo and Sarah Scagliarini and Thomas B{\"u}ttner and Giuseppe Fornarini and Myint, \{Zin W.\} and Luca Galli and Souza, \{Vinicius Carrera\} and Renate Pichler and \{De Giorgi\}, Ugo and Nathalia Gandur and Lam, \{Elaine T.\} and Danielle Gilbert and Lazar Popovic and Enrique Grande and Giulia Mammone and Rossana Berardi and Crabb, \{Simon J.\} and Robert Kemp and Javier Molina-Cerrillo and Marcelo Freitas and Murilo Luz and Roberto Iacovelli and Fabio Calabr{\`o} and Deniz Tural and Francesco Atzori and Zs{\'o}fia K{\"u}ronya and Rita Chiari and Saul Campos and Orazio Caffo and Fay, \{Andr{\'e} P.\} and Jakub Kucharz and Zucali, \{Paolo Andrea\} and Rinck, \{Jos{\'e} Augusto\} and Annalisa Zeppellini and Bastos, \{Diogo Assed\} and Gaetano Aurilio and Augusto Mota and Karine Trindade and Cinzia Ortega and Sade, \{Juan Pablo\} and Mimma Rizzo and Ond{\v r}ej Fiala and Nuno Vau and Patrizia Giannatempo and Allan Barillas and Monteiro, \{Fernando Sabino M.\} and Breno Dauster and Alessia Mennitto and Lucas Nogueira and \{de Carvalho Fernandes\}, Roni and Emmanuel Seront and Aceituno, \{Lu{\'i}s Garcia\} and Francesco Grillone and Cutuli, \{Hernan Javier\} and Mauricio Fernandez and Maria Bassanelli and Kopp, \{Ray Manneh\} and Giandomenico Roviello and Halima Abahssain and Giuseppe Procopio and Michele Milella and Jindrich Kopecky and Angelo Martignetti and Carlo Messina and Manuel Caitano and Eva Inman and Ravindran Kanesvaran and Daniel Herchhorn and Daniele Santini and Aristotelis Bamias and Renato Bisonni and Alessandra Mosca and Franco Morelli and Fernando Maluf and Andrey Soares and Fernando Nunes and Alvaro Pinto and Anca Zgura and Lorena Incorvaia and Jawaher Ansari and Zabalza, \{Ignacio Ortego\} and Johannes Landmesser and Alessandro Rizzo and Veronica Mollica and Andrea Marchetti and Matteo Rosellini and Giulia Sorgentoni and Nicola Battelli and Sebastiano Buti and Camillo Porta and Joaquim Bellmunt",

note = "Publisher Copyright: {\textcopyright} The Author(s) 2024.",

year = "2024",

month = jun,

doi = "10.1007/s00262-024-03682-w",

language = "English",

volume = "73",

number = "6",

}

Massari, F, Santoni, M, Takeshita, H, Okada, Y, Tapia, JC, Basso, U, Maruzzo, M, Scagliarini, S, Büttner, T, Fornarini, G, Myint, ZW, Galli, L, Souza, VC, Pichler, R, De Giorgi, U, Gandur, N, Lam, ET, Gilbert, D, Popovic, L, Grande, E, Mammone, G, Berardi, R, Crabb, SJ, Kemp, R, Molina-Cerrillo, J, Freitas, M, Luz, M, Iacovelli, R, Calabrò, F, Tural, D, Atzori, F, Küronya, Z, Chiari, R, Campos, S, Caffo, O, Fay, AP, Kucharz, J, Zucali, PA, Rinck, JA, Zeppellini, A, Bastos, DA, Aurilio, G, Mota, A, Trindade, K, Ortega, C, Sade, JP, Rizzo, M, Fiala, O, Vau, N, Giannatempo, P, Barillas, A, Monteiro, FSM, Dauster, B, Mennitto, A, Nogueira, L, de Carvalho Fernandes, R, Seront, E, Aceituno, LG, Grillone, F, Cutuli, HJ, Fernandez, M, Bassanelli, M, Kopp, RM, Roviello, G, Abahssain, H, Procopio, G, Milella, M, Kopecky, J, Martignetti, A, Messina, C, Caitano, M, Inman, E, Kanesvaran, R, Herchhorn, D, Santini, D, Bamias, A, Bisonni, R, Mosca, A, Morelli, F, Maluf, F, Soares, A, Nunes, F, Pinto, A, Zgura, A, Incorvaia, L, Ansari, J, Zabalza, IO, Landmesser, J, Rizzo, A, Mollica, V, Marchetti, A, Rosellini, M, Sorgentoni, G, Battelli, N, Buti, S, Porta, C & Bellmunt, J 2024, 'Global real-world experiences with pembrolizumab in advanced urothelial carcinoma after platinum-based chemotherapy: the ARON-2 study', Cancer Immunology, Immunotherapy, vol. 73, no. 6, 106. https://doi.org/10.1007/s00262-024-03682-w

TY - JOUR

T1 - Global real-world experiences with pembrolizumab in advanced urothelial carcinoma after platinum-based chemotherapy

T2 - the ARON-2 study

AU - Massari, Francesco

AU - Santoni, Matteo

AU - Takeshita, Hideki

AU - Okada, Yohei

AU - Tapia, Jose Carlos

AU - Basso, Umberto

AU - Maruzzo, Marco

AU - Scagliarini, Sarah

AU - Büttner, Thomas

AU - Fornarini, Giuseppe

AU - Myint, Zin W.

AU - Galli, Luca

AU - Souza, Vinicius Carrera

AU - Pichler, Renate

AU - De Giorgi, Ugo

AU - Gandur, Nathalia

AU - Lam, Elaine T.

AU - Gilbert, Danielle

AU - Popovic, Lazar

AU - Grande, Enrique

AU - Mammone, Giulia

AU - Berardi, Rossana

AU - Crabb, Simon J.

AU - Kemp, Robert

AU - Molina-Cerrillo, Javier

AU - Freitas, Marcelo

AU - Luz, Murilo

AU - Iacovelli, Roberto

AU - Calabrò, Fabio

AU - Tural, Deniz

AU - Atzori, Francesco

AU - Küronya, Zsófia

AU - Chiari, Rita

AU - Campos, Saul

AU - Caffo, Orazio

AU - Fay, André P.

AU - Kucharz, Jakub

AU - Zucali, Paolo Andrea

AU - Rinck, José Augusto

AU - Zeppellini, Annalisa

AU - Bastos, Diogo Assed

AU - Aurilio, Gaetano

AU - Mota, Augusto

AU - Trindade, Karine

AU - Ortega, Cinzia

AU - Sade, Juan Pablo

AU - Rizzo, Mimma

AU - Fiala, Ondřej

AU - Vau, Nuno

AU - Giannatempo, Patrizia

AU - Barillas, Allan

AU - Monteiro, Fernando Sabino M.

AU - Dauster, Breno

AU - Mennitto, Alessia

AU - Nogueira, Lucas

AU - de Carvalho Fernandes, Roni

AU - Seront, Emmanuel

AU - Aceituno, Luís Garcia

AU - Grillone, Francesco

AU - Cutuli, Hernan Javier

AU - Fernandez, Mauricio

AU - Bassanelli, Maria

AU - Kopp, Ray Manneh

AU - Roviello, Giandomenico

AU - Abahssain, Halima

AU - Procopio, Giuseppe

AU - Milella, Michele

AU - Kopecky, Jindrich

AU - Martignetti, Angelo

AU - Messina, Carlo

AU - Caitano, Manuel

AU - Inman, Eva

AU - Kanesvaran, Ravindran

AU - Herchhorn, Daniel

AU - Santini, Daniele

AU - Bamias, Aristotelis

AU - Bisonni, Renato

AU - Mosca, Alessandra

AU - Morelli, Franco

AU - Maluf, Fernando

AU - Soares, Andrey

AU - Nunes, Fernando

AU - Pinto, Alvaro

AU - Zgura, Anca

AU - Incorvaia, Lorena

AU - Ansari, Jawaher

AU - Zabalza, Ignacio Ortego

AU - Landmesser, Johannes

AU - Rizzo, Alessandro

AU - Mollica, Veronica

AU - Marchetti, Andrea

AU - Rosellini, Matteo

AU - Sorgentoni, Giulia

AU - Battelli, Nicola

AU - Buti, Sebastiano

AU - Porta, Camillo

AU - Bellmunt, Joaquim

PY - 2024/6

Y1 - 2024/6

N2 - 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.

AB - 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.

KW - ARON-2 study

KW - Pembrolizumab

KW - Real-world data

KW - Survival

KW - Tumor response

KW - Urothelial cancer

UR - https://www.scopus.com/pages/publications/85190701306

UR - https://www.scopus.com/pages/publications/85190701306#tab=citedBy

U2 - 10.1007/s00262-024-03682-w

DO - 10.1007/s00262-024-03682-w

M3 - Article

C2 - 38634928

AN - SCOPUS:85190701306

SN - 0340-7004

VL - 73

JO - Cancer Immunology, Immunotherapy

JF - Cancer Immunology, Immunotherapy

IS - 6

M1 - 106

ER -