Bone targeting agents, but not radiation therapy, improves survival in patients with bone metastases from advanced urothelial carcinoma receiving pembrolizumab: results from the ARON-2 study

Santoni, Matteo;Massari, Francesco;Takeshita, Hideki;Tapia, Jose;Kopecky, Jindrich;et.al.
(2023) Clinical and Experimental Medicine (Print) — Vol. 23, n° 8, p. 5413-5422 (2023)

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Authors
  • Santoni, Matteo
    Author
  • Massari, Francesco
    Author
  • Takeshita, Hideki
    Author
  • Tapia, Jose
    Author
  • Seront, EmmanuelUCLouvain
    Author
  • Kopecky, Jindrich
    Author
  • et. al.
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Abstract
The ARON-2 study (NCT05290038) aimed to assess the real-world efficacy of pembrolizumab in patients recurred or progressed after platinum-based chemotherapy. This retrospective analysis reports the outcomes of urothelial carcinoma (UC) patients with bone metastases (BM). Medical records of patients with documented metastatic UC treated by pembrolizumab as second-line therapy were reviewed from60 institutions in 20 countries. Patients were assessed for Overall Response Rate (ORR), Progression-Free Survival (PFS), and Overall Survival (OS). Univariate and multivariate analyses were used to explore the association of variables of interest with OS and PFS. 881 patients were included; of them, 263 (30%) presented BM. Median follow-up time was 22.7 months. Patients with BM showed both shorter median OS (5.9 months vs 13.1 months, p < 0.001) and PFS (3.5 months, vs 7.3 months, p < 0.001) compared to patients without BM. Patients who received bone targeted agents (BTAs) showed a significantly longer median OS (8.5 months vs 4.6 months, p = 0.003) and PFS (6.1 months vs 3.2 months, p = 0.003), while no survival benefits were observed among patients who received radiation therapy for BM during pembrolizumab treatment compared to those who did not. In multivariate analysis, performance status, concomitant liver metastases, and the lack of use of BTAs were significantly associated with worse OS and PFS. Bone involvement in UC patients treated with pembrolizumab predicts inferior survival. Poor performance status and liver metastases may further worsen outcomes, while the use of BTAs is associated with improved outcomes.
Affiliations
  • Macerata Hospital, via Santa Lucia 2, 62100 Macerata, ItalyOncology Unit
  • IRCCS Azienda Ospedaliero-Universitaria di Bologna, Via Albertoni ‑ 15, Bologna, ItalyMedical Oncology
  • Saitama Medical Center, Saitama Medical University, Saitama, JapanDepartment of Urology
  • Institut d’Investigació Biomèdica Sant Pau, Hospital de la Santa Creui Sant Pau, Barcelona, SpainDepartment of Medical Oncology
  • Department of Oncology, Istituto Oncologico Veneto IOV - IRCCS, 35128 Padua, ItalyMedical Oncology 1 Unit
  • Medical University of Innsbruck, Anichstrasse 35, 6020 Innsbruck, AustriaDepartment of Urology
  • A.O.U. Consorziale Policlinico di Bari, Bari, ItalyDivision of Medical Oncology
  • Aurora, CO, USAUniversity of Colorado Anschutz Medical Campus
  • MD Anderson Cancer Center Madrid, Madrid, SpainDepartment of Medical Oncology
  • University of Southampton, Southampton, UKSouthampton Experimental Cancer Medicine Centre
  • Hospital Ramón y Cajal, Madrid, SpainDepartment of Medical Oncology
  • San Camillo Forlanini Hospital, Rome, ItalyDepartment of Oncology
  • Bakirköy Dr.SadiKonuk Training and Research Hospital, Zuhuratbaba District, TevfikSaglam St. No: 11, Bakirkoy, Istanbul, TurkeyDepartment of Medical Oncology
  • National Institute of Oncology, Budapest, HungaryDepartment of Genitourinary Medical Oncology and Clinical Pharmacology
  • Maria Sklodowska-Curie National Research Institute of Oncology, Warsaw, PolandDepartment of Uro‑Oncology
  • Charles University, Pilsen, Czech RepublicDepartment of Oncology and Radiotherapeutics, Faculty of Medicine and University Hospital in Pilsen
  • Charles University, alejSvobody 76, Pilsen, Czech RepublicBiomedical Center, Faculty of Medicine in Pilsen
  • Sociedad de Oncología y Hematología del Cesar, Valledupar, ColombiaClinical Oncology
  • National Institute of Oncology, Medical Oncology Unit, Mohamed V University, Rabat, MoroccoMedicine and Pharmacy Faculty
  • University Hospital Hradec Kralove, Hradec Kralove, Czech RepublicDepartment of Clinical Oncology and Radiotherapy
  • Località Campostaggia s.n.c., 53036 Poggibonsi, ItalyDipartimento oncologico usl sud‑est toscana‑area senese
  • Singapore, SingaporeNational Cancer Centre Singapore
  • ATTIKON University Hospital, National and Kapodistrian University of Athens, Athens, Greece2nd Propaedeutic Department of Internal Medicine, School of Medicine
  • Tawam Hospital, Al Ain, United Arab EmiratesMedical Oncology
  • Ratzeburger Allee 160, 23538 Lübeck, GermanyKlinik fürUrologie
  • Interdisciplinary Department of Medicine, University of Bari “Aldo Moro”, Bari, ItalyChair of Oncology
  • Harvard Medical School, Boston, MA, USADana Farber Cancer Institute
  • King Hussein Cancer Center, Amman, JordanDepartment of Medical Oncology
  • Policlinico Umberto I, Sapienza, University of Rome, Rome, ItalyUOC Oncologia A
  • Centre Hospitalier de Jolimont, BelgiumDepartment of Medical Oncology

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Santoni, M., Massari, F., Takeshita, H., Tapia, J., Dionese, M., Pichler, R., Rizzo, M., Lam, E., Grande, E., Kemp, R., Molina-Cerrillo, J., Calabrò, F., Tural, D., Küronya, Z., Kucharz, J., Fiala, O., Seront, E., Kopp, R., Abahssain, H., et al. (2023). Bone targeting agents, but not radiation therapy, improves survival in patients with bone metastases from advanced urothelial carcinoma receiving pembrolizumab: results from the ARON-2 study. Clinical and Experimental Medicine (Print), 23(8), 5413-5422. https://doi.org/10.1007/s10238-023-01235-6 (Original work published 2023)