Toxicity‐related immunotherapy discontinuation and outcome in patients with advanced renal cell carcinoma treated with immune‐based combinations ( <scp>ARON</scp> ‐1 study)
The advent of immunotherapy (IO) has revolutionized the therapeutic landscape of advanced renal cell carcinoma (RCC). The aim of this study is to analyze clinical outcomes in patients who discontinued IO in metastatic RCC first line in a real-world setting. We retrospectively collected data about 1077 patients aged ≥18 years with a histologically confirmed diagnosis of clear cell RCC and histologically or radiologically confirmed metastatic disease, treated in 52 centers from 20 countries, between January 1, 2016 and April 1, 2024, from all three International metastatic renal cell carcinoma (mRCC) Database Consortium risk groups (favorable, intermediate, and poor). Each patient was treated in front-line with IO + Tirosine Kinase Inhibitor or IO + IO combinations. In this study we analyzed survival outcomes comparing patients who interrupted IO versus patients who continuously received it and multivariable analysis. We analyzed the clinical behavior of 185 patients who interrupted IO treatment due to SAE, 127 patients with IO-tyrosine kinase inhibitor, 58 patients with IO-IO versus 892 patients who do not discontinue IO treatment. No significant differences in OS were found in patients who discontinue treatment versus no discontinuation. Moreover, time to discontinuation seemed to be an OS predictor, being inferior in patients who interrupted IO in the first to third month versus patients who discontinued treatment after this time data. The ARON-1 study offers a comprehensive examination of toxicity-related IO discontinuation in advanced RCC, contributing to a better understanding of balancing treatment efficacy with tolerability.
Authors
- Maria Teresa Bourlon (ORCID: https://orcid.org/0000-0002-3116-912X)
- Martina Catalano (ORCID: https://orcid.org/0000-0003-1856-2848)
- Tarek Taha (ORCID: https://orcid.org/0000-0001-7936-5245)
- Ondřej Fiala (ORCID: https://orcid.org/0000-0002-4096-7385)
- Linda Cerbone (ORCID: https://orcid.org/0000-0003-1339-4056)
- Sebastiano Buti (ORCID: https://orcid.org/0000-0003-0876-0226)
- Camillo Porta (ORCID: https://orcid.org/0000-0003-2412-1563)
- Rita Chiari (ORCID: https://orcid.org/0000-0002-7649-273X)
- Matteo Santoni (ORCID: https://orcid.org/0000-0001-7340-6173)
- Jakub Kucharz (ORCID: https://orcid.org/0000-0001-5388-8910)
- Andrey Soares (ORCID: https://orcid.org/0000-0003-4980-6729)
- Marwan G. Ghosn (ORCID: https://orcid.org/0000-0003-1627-384X)
- Giandomenico Roviello (ORCID: https://orcid.org/0000-0001-5504-8237)
- Enrique Grande (ORCID: https://orcid.org/0000-0002-0134-4732)
- Javier Molina‐Cerrillo (ORCID: https://orcid.org/0000-0003-4616-0598)
- Emmanuel Seront (ORCID: https://orcid.org/0000-0003-4807-7472)
- Mimma Rizzo (ORCID: https://orcid.org/0000-0001-7743-741X)
- Kaisa Sunela (ORCID: https://orcid.org/0000-0002-2639-5448)
- Se Hoon Park (ORCID: https://orcid.org/0000-0001-5084-9326)
- Alessandra Filosa (ORCID: https://orcid.org/0000-0002-4071-4898)
- Sergio Bracarda (ORCID: https://orcid.org/0000-0002-0703-2959)
- Annalisa Zeppellini (ORCID: https://orcid.org/0009-0002-2137-3140)
- Francesco Massari (ORCID: https://orcid.org/0000-0001-6476-6871)
- Yüksel Ürün (ORCID: https://orcid.org/0000-0002-9152-9887)
- Fernando Sabino Marques Monteiro (ORCID: https://orcid.org/0000-0002-6621-8251)
- Sarah Scagliarini (ORCID: https://orcid.org/0000-0001-5814-2296)
- Anca Florina Zgura (ORCID: https://orcid.org/0000-0002-2370-5762)
- Jawaher Ansari (ORCID: https://orcid.org/0000-0001-5525-548X)
- Hana Študentová (ORCID: https://orcid.org/0000-0003-2105-9258)
- Haoran Li (ORCID: https://orcid.org/0000-0001-9993-6842)
Institutions
- Marche Polytechnic University (IT)
- University of Parma (IT)
- Cliniques Universitaires Saint-Luc (BE)
- Royal Marsden NHS Foundation Trust (GB)
- Carol Davila University of Medicine and Pharmacy (RO)
- Saint Joseph University (LB)
- Charles University (CZ)
- Hospital Israelita Albert Einstein (BR)
- Samsung Medical Center (KR)
- Eastern Cooperative Oncology Group (US)
- Ospedale Antonio Cardarelli (IT)
- Tawam Hospital (AE)
- Azienda Socio Sanitaria Territoriale Grande Ospedale Metropolitano Niguarda (IT)
- Azienda Universitaria Ospedaliera Consorziale - Policlinico Bari (IT)
- The University of Kansas Cancer Center (US)
- Instituto Nacional de Ciencias Médicas y Nutrición Salvador Zubirán (MX)
- Ospedali Riuniti Marche Nord (IT)
- Azienda USL di Bologna (IT)
- National Institute of Oncology (HU)
- Azienda Ospedaliera S.Maria (IT)
- Institutul Oncologic Bucuresti (RO)
- Tampere University Hospital (FI)
- Tampere University (FI)
- Nini Hospital (LB)
- Hospital Sírio-Libanês (BR)
- The Maria Sklodowska-Curie National Research Institute of Oncology (PL)
- Carlo Forlanini Hospital (IT)
- MD Anderson Cancer Center Madrid (ES)
- Hospital Universitario Ramón y Cajal (ES)
- Ospedale di Macerata
- University of Florence (IT)
- University of Macerata (IT)
- University of Bari Aldo Moro (IT)
- Palacký University Olomouc (CZ)
- Universidad Panamericana (MX)
- University of Bologna (IT)
Publication Details
- Journal
- International Journal of Cancer
- Published
- 2025-11-04
- DOI
- https://doi.org/10.1002/ijc.70228
- Citations
- 2
- Primary Topic
- Renal cell carcinoma treatment
- Type
- article
- Field-Weighted Citation Impact
- 3.04