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Multicenter Study
. 2024 Aug 27;14(1):19802.
doi: 10.1038/s41598-024-70182-3.

Radiotherapy plus pembrolizumab for advanced urothelial carcinoma: results from the ARON-2 real-world study

Mimma Rizzo #  1 , Andrey Soares #  2   3 , Enrique Grande  4 , Aristotelis Bamias  5 , Ray Manneh Kopp  6 , Edoardo Lenci  7 , Thomas Buttner  8 , Samer Salah  9 , Francesco Grillone  10 , Icaro Thiago de Carvalho  11 , Jose Carlos Tapia  12 , Calogero Gucciardino  13 , Alvaro Pinto  14 , Alessia Mennitto  15 , Halima Abahssain  16 , Pasquale Rescigno  17 , Zin Myint  18 , Hideki Takeshita  19 , Gian Paolo Spinelli  20 , Lazar Popovic  21 , Maria Giuseppa Vitale  22 , Ondrej Fiala  23   24 , Patrizia Giannatempo  25 , Roubini Zakopoulou  5 , Francesco Carrozza  26 , Francesco Massari  27 , Fernando Sabino Marques Monteiro  28 , Maria Paola Pace  29 , Massimo Giannini  29 , Giandomenico Roviello  30 , Camillo Porta  31   32 , Nicola Battelli  33 , Ravindran Kanesvaran  34 , Matteo Santoni  33
Affiliations
Multicenter Study

Radiotherapy plus pembrolizumab for advanced urothelial carcinoma: results from the ARON-2 real-world study

Mimma Rizzo et al. Sci Rep. .

Abstract

The addition of metastasis-directed radiotherapy (MDRT) to immunotherapy in patients with advanced urothelial carcinoma (aUC) has shown promising results. We report the real-world data from the ARON-2 study (NCT05290038) on the impact of conventional (CRT) or stereotactic body radiotherapy (SBRT) on the outcome of aUC patients receiving pembrolizumab after platinum-based-chemotherapy. Medical records of 837 patients were reviewed from 60 institutions in 20 countries. Two hundred and sixty-two patients (31%) received radiotherapy (cohort A), of whom 193 (23%) received CRT and 69 (8%) received SBRT. Patients were assessed for overall survival (OS), progression-free survival (PFS), and overall response rate (ORR). Univariate and multivariate analyses were used to explore the association of variables of interest with OS and PFS. With a median follow-up of 22.7 months, the median OS was 10.2 months, 6.8 months and 16.0 months in no RT, CRT and SBRT subgroups (p = 0.005), with an 1y-OS rates of 47%, 34% and 61%, respectively (p < 0.001). The 1y-OS rate in the SBRT subgroup were significantly higher for both lower (63%) and upper tract UC (68%), for pure urothelial histology (63%) and variant histologies (58%), and for patients with bone (40%) and lymph-node metastases (61%). Median PFS was 4.8 months, 9.6 months and 5.8 months in the CRT, SBRT and no RT subgroups, respectively (p = 0.060). The 1y-PFS rate was significantly higher (48%) in the SBRT population and was confirmed in all patient subsets. The difference in terms of ORR was in favour of SBRT. Our real-world analysis showed that the use of SBRT/pembrolizumab combination may play a role in a subset of aUC patients to increase disease control and possibly overall survival.

Keywords: ARON-2 study; Pembrolizumab; Radiation therapy; Real-world data; Stereotactic radiation therapy; Urothelial carcinoma.

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Conflict of interest statement

Mimma Rizzo has received honoraria as a speaker/consultant by MSD, Astrazeneca, Bristol-Myers Squibb, Gilead, Janssen and Merck Serono, all unrelated to the present paper. Andrey Soares has received Honoraria: Janssen, Pfizer, Bayer, AstraZeneca, Astellas Pharma, Merck Serono, Sanofi, Ipsen, Adium; Consulting or Advisory Role: Astellas Pharma, Janssen, Roche, Bayer, AstraZeneca, MSD, Bristol-Myers Squibb, Adium, Ipsen; Research Funding: Bristol-Myers Squibb (Inst), Astellas (Inst), AstraZeneca (Inst); Travel, Accommodations, Expenses: Bayer, Janssen, Ipsen, Adium, MSD. 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. Ondrej Fiala received honoraria from Roche, Janssen, MSD, Pierre Fabre, GSK and Pfizer for consultations and lectures unrelated to this project. Patrizia Giannatempo has received research support from Ipsen, Astra Zeneca e MSD and honoraria for speaker engagements, advisory roles from Astellas, MSD, Janssen, Pfizer. Francesco Massari has received research support and/or honoraria from Astellas, BMS, Janssen, Ipsen, MSD and Pfizer outside the submitted work. 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, Exelixis, Ipsen, Merck and MSD and acted as a Protocol Steering Committee Member for BMS, Eisai and MSD. Ravindran 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. Matteo Santoni has received research support and honoraria from Janssen, Bristol Myers Squibb, Ipsen, MSD, Astellas and Bayer, all unrelated to the present paper. The other authors have no relevant financial or non-financial interests to disclose.

Figures

Figure 1
Figure 1
Median Overall Survival in the overall study population and in patients with tumors of the lower urinary tract, pure urothelial carcinoma (UC) histology or lymph node metastases.
Figure 2
Figure 2
Overall Survival (1y-OS rate) and Progression-Free Survival rate at 1y (1y-PFS rate) stratified by clinico-pathological characteristics.
See this image and copyright information in PMC

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