Skip to main page content
U.S. flag

An official website of the United States government

Dot gov

The .gov means it’s official.
Federal government websites often end in .gov or .mil. Before sharing sensitive information, make sure you’re on a federal government site.

Https

The site is secure.
The https:// ensures that you are connecting to the official website and that any information you provide is encrypted and transmitted securely.

Access keys NCBI Homepage MyNCBI Homepage Main Content Main Navigation
. 2024 Apr 18;73(6):106.
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 #  1 , Matteo Santoni #  2 , Hideki Takeshita  3 , Yohei Okada  3 , Jose Carlos Tapia  4 , Umberto Basso  5 , Marco Maruzzo  5 , Sarah Scagliarini  6 , Thomas Büttner  7 , Giuseppe Fornarini  8 , Zin W Myint  9 , Luca Galli  10 , Vinicius Carrera Souza  11   12 , Renate Pichler  13 , Ugo De Giorgi  14 , Nathalia Gandur  12   15 , Elaine T Lam  16 , Danielle Gilbert  16 , Lazar Popovic  17 , Enrique Grande  18 , Giulia Mammone  19 , Rossana Berardi  20 , Simon J Crabb  21 , Robert Kemp  21 , Javier Molina-Cerrillo  22 , Marcelo Freitas  12   23 , Murilo Luz  12   24 , Roberto Iacovelli  25 , Fabio Calabrò  26 , Deniz Tural  27 , Francesco Atzori  28 , Zsófia Küronya  29 , Rita Chiari  30 , Saul Campos  12   31 , Orazio Caffo  32 , André P Fay  12   33 , Jakub Kucharz  34 , Paolo Andrea Zucali  35   36 , José Augusto Rinck  12   37 , Annalisa Zeppellini  38 , Diogo Assed Bastos  12   39 , Gaetano Aurilio  40 , Augusto Mota  12   41 , Karine Trindade  12   42 , Cinzia Ortega  43 , Juan Pablo Sade  44 , Mimma Rizzo  45 , Ondřej Fiala  46 , Nuno Vau  47 , Patrizia Giannatempo  48 , Allan Barillas  12   49 , Fernando Sabino M Monteiro  12   50 , Breno Dauster  12   51 , Alessia Mennitto  52 , Lucas Nogueira  12   53 , Roni de Carvalho Fernandes  12   54 , Emmanuel Seront  55 , Luís Garcia Aceituno  12   56 , Francesco Grillone  57 , Hernan Javier Cutuli  12   58 , Mauricio Fernandez  12   59 , Maria Bassanelli  60 , Ray Manneh Kopp  61 , Giandomenico Roviello  62 , Halima Abahssain  63 , Giuseppe Procopio  48   64 , Michele Milella  65 , Jindrich Kopecky  66 , Angelo Martignetti  67 , Carlo Messina  68 , Manuel Caitano  12   69 , Eva Inman  12   70 , Ravindran Kanesvaran  71 , Daniel Herchhorn  12   72 , Daniele Santini  73 , Aristotelis Bamias  74 , Renato Bisonni  75 , Alessandra Mosca  76 , Franco Morelli  77 , Fernando Maluf  12   78 , Andrey Soares  12   79 , Fernando Nunes  12   80 , Alvaro Pinto  81 , Anca Zgura  82 , Lorena Incorvaia  83 , Jawaher Ansari  84 , Ignacio Ortego Zabalza  18 , Johannes Landmesser  85 , Alessandro Rizzo  86 , Veronica Mollica  87 , Andrea Marchetti  87 , Matteo Rosellini  87 , Giulia Sorgentoni  2 , Nicola Battelli  2 , Sebastiano Buti  88 , Camillo Porta  89 , Joaquim Bellmunt  90
Affiliations

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

Francesco Massari et al. Cancer Immunol Immunother. .

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.

PubMed Disclaimer

Conflict of interest statement

Matteo Santoni has received research support and honoraria from Janssen, Bristol Myers Squibb, Ipsen, MSD, Astellas and Bayer, all unrelated to the present paper. Francesco Massari has received research support and/or honoraria from Astellas, BMS, Janssen, Ipsen, MSD and Pfizer outside the submitted work. R. Kanesvaran has received fees for speaker bureau and advisory board activities from the following companies; Pfizer, MSD, BMS, Eisai, Ipsen, Johnson and Johnson, Merck, Amgen, Astellas and Bayer. Enrique Grande has received honoraria for speaker engagements, advisory roles or funding of continuous medical education from Adacap, AMGEN, Angelini, Astellas, Astra Zeneca, Bayer, Blueprint, Bristol Myers Squibb, Caris Life Sciences, Celgene, Clovis-Oncology, Eisai, Eusa Pharma, Genetracer, Guardant Health, HRA-Pharma, IPSEN, ITM-Radiopharma, Janssen, Lexicon, Lilly, Merck KGaA, MSD, Nanostring Technologies, Natera, Novartis, ONCODNA (Biosequence), Palex, Pharmamar, Pierre Fabre, Pfizer, Roche, Sanofi-Genzyme, Servier, Taiho and Thermo Fisher Scientific. EG has received research grants from Pfizer, Astra Zeneca, Astellas and Lexicon Pharmaceuticals. Fernando Sabino Marques Monteiro has received research support from Janssen, Merck Sharp Dome and honoraria from Janssen, Ipsen, Bristol Myers Squibb and Merck Sharp Dome. Camillo Porta has received honoraria from Angelini Pharma, AstraZeneca, BMS, Eisai, General Electric, Ipsen and MSD and acted as a Protocol Steering Committee Member for BMS, Eisai and MSD. Sebastiano Buti received honoraria as speaker at scientific events and advisory role by BMS, Pfizer, MSD, Ipsen, AstraZeneca, Merck. Joaquim Bellmunt reports institutional and personal, paid and unpaid support for research, advisory boards, consultancy and honoraria (all outside this work) from: AstraZeneca, Bristol Myers Squibb, EMD Serono, Merck, Pfizer, Roche, Sanofi/Aventis, Up-To-Date, CME events (Peerview, OncLive,), outside the submitted work. No speaker’s bureau. Javier Molina-Cerrillo declares consultant, advisory or speaker roles for IPSEN, Roche, Pfizer, Sanofi, Janssen and BMS. JMC has received research grants from Pfizer, IPSEN and Roche. Jose Carlos Tapia has received travel, accommodations, expenses from Roche, Pfizer, Merck and Lily. Zin Myint has received research support from Merck but not related to the present paper. Patrizia Giannatempo has received research support from Ipsen, Astra Zeneca e MSD and honoraria for speaker engagements, advisory roles from Astellas, MSD, Janssen, Pfizer. The other authors declare to have no conflicts of interest.

Figures

Fig. 1
Fig. 1
Overall and progression-free survival curves in the overall ARON-2 study population
Fig. 2
Fig. 2
Overall survival in patients treated with pembrolizumab stratified by pembrolizumab setting (cohort A: patients progressed during first-line platinum base chemotherapy; cohort B: patients recurred within < 1y since the completion of adjuvant/neoadjuvant therapy), sex, smoking attitude and ECOG-PS
Fig. 3
Fig. 3
Overall survival in patients treated with pembrolizumab stratified by synchronous or metachronous metastatic disease, bone or liver metastases or visceral metastases
Fig. 4
Fig. 4
Progression-free survival in patients treated with pembrolizumab stratified by pembrolizumab setting (cohort A: patients progressed during first-line platinum base chemotherapy; cohort B: patients recurred within < 1y since the completion of adjuvant/neoadjuvant therapy), ECOG-PS, synchronous or metachronous metastatic disease, visceral metastases, bone or liver metastases
Fig. 5
Fig. 5
Overall survival and progression-free survival in patients stratified by ARON score
See this image and copyright information in PMC

References

    1. https://gco.iarc.fr/ Accessed on October 8th, 2022
    1. Mohanty SK, Lobo A, Cheng L. The 2022 revision of World Health Organization classification of tumors of the urinary system and male genital organs: advances and challenges. Hum Pathol. 2022;S0046–8177(22):00224–226. - PubMed
    1. Cronin KA, Lake AJ, Scott S, Sherman RL, Noone AM, Howlader N, et al. Annual report to the Nation on the status of cancer, part I: national cancer statistics. Cancer. 2018;124(13):2785–2800. doi: 10.1002/cncr.31551. - DOI - PMC - PubMed
    1. Mollica V, Rizzo A, Montironi R, Cheng L, Giunchi F, Schiavina R, et al. Current strategies and novel therapeutic approaches for metastatic urothelial carcinoma. Cancers (Basel) 2020;12(6):1449. doi: 10.3390/cancers12061449. - DOI - PMC - PubMed
    1. Powles T, Smith K, Stenzl A, Bedke J. Immune checkpoint inhibition in metastatic urothelial cancer. EurUrol. 2017;72:477–481. - PubMed

Publication types