Objective: Our multicenter retrospective real-world study aims to assess the prevalence and clinicopathological characteristics of Pref patients.
Methods: This study collected data from 72 centers across 22 countries (1709 patients), involving patients aged ≥18 with metastatic clear cell RCC. All enrolled patients were treated with first-line IO combinations. Data included patient demographics, histology, metastatic sites, and treatment responses. Radiological assessments followed Response Evaluation Criteria in Solid Tumors 1.1. Statistical analyses employed Kaplan-Meier, Cox proportional hazard models, logistic regression, and Receiver Operating Characteristic (ROC) curve analysis.
Results: In our study, Pref rate was 19%. Nivolumab/ipilimumab showed the highest Pref rate (27%), while pembrolizumab/lenvatinib exhibited the lowest (10%). Pref patients demonstrated significantly lower median overall survival (OS - 7.6 months) compared to non-Pref patients (55.7 months), p<0.001. At the multivariate analysis nephrectomy, sarcomatoid de-differentiation, intermediate/poor International Metastatic RCC Database Consortium (IMDC) risk, bone and brain metastases emerged as significant predictors of OS for Pref RCC patients. Logistic regression showed a significant relationship between liver metastases, intermediate/poor IMDC risk, no surgery, and an increased risk of Pref. This study presents limitations, mainly due to its retrospective design.
Conclusions: The ARON-1 study provides valuable insights into Pref patients, emphasizing the challenges of this precociously resistant subgroup. Identified predictors could guide risk stratification, aiding clinicians in tailored therapeutic approaches.
Written by: Daniele Santini,1 Haoran Li,2 Giandomenico Roviello,3 Se Hoon Park,4 Enrique Grande,5 Jakub Kucharz,6 Umberto Basso,7 Ondrej Fiala,8,9 Fernando Sabino Marques Monteiro,10,11 Alexandr Poprach,12 Sebastiano Buti,13 Javier Molina-Cerrillo,14 Martina Catalano,3 Tomas Buchler,15 Emmanuel Seront,16 Jawaher Ansari,17 Zin W. Myint,18 Marwan Ghosn,19 Fabio Calabrò,20 Ray Manneh Kopp,21 Dipen Bhuva,22 Maria T. Bourlon,23 Michela Roberto,24 Mattia Alberto Di Civita,24,25 Veronica Mollica,26 Andrea Marchetti,26,27 Andrey Soares,28,10 Nicola Battelli,29 Marco Ricci,30 Ravindran Kanesvaran,31 Aristotelis Bamias,32 Camillo Porta,33 Francesco Massari,26,27 Matteo Santoni,29
- Department of Radiological, Oncological and Pathological Sciences, Policlinico Umberto I, University of Rome, Sapienza Rome, Italy
- Department of Internal Medicine, Division of Medical Oncology, University of Kansas Cancer Center, Westwood, KS, USA
- Department of Health Sciences, Section of Clinical Pharmacology and Oncology, University of Florence, Florence, Italy
- Division of Hematology-Oncology, Department of Medicine, Samsung Medical Center, Sungkyunkwan University School of Medicine, Seoul, Korea
- Department of Medical Oncology, MD Anderson Cancer Center Madrid, Madrid, Spain
- Department of Uro-Oncology, Maria Sklodowska-Curie National Research Institute of Oncology Warsaw, Warsaw, Poland
- Medical Oncology 1 Unit, Department of Oncology, Istituto Oncologico Veneto IOV IRCCS, Padova, Italy
- Department of Oncology and Radiotherapeutics, Faculty of Medicine and University Hospital in Pilsen, Charles University, Czech Republic
- Biomedical Center, Faculty of Medicine in Pilsen, Charles University, Pilsen, Czech Republic
- Latin American Cooperative Oncology Group - LACOG
- Hospital Sírio-Libanês, Brasília, DF, Brazil
- Masaryk Memorial Cancer Institute, Brno, Czech Republic, Faculty of Medicine, Masaryk University, Brno, Czech Republic
- Department of Medicine and Surgery, University of Parma - Oncology Unit, University Hospital of Parma, Italy
- Department of Medical Oncology, Hospital Ramón y Cajal, Madrid, Spain
- Department of Oncology, Second Faculty of Medicine, Charles University and University Hospital Motol, Prague, Czech Republic
- Department of Medical Oncology, Cliniques Universitaires Saint-Luc, Brussels, Belgium
- Medical Oncology, Tawam Hospital, Al Ain, United Arab Emirates
- Markey Cancer Center, University of Kentucky, Lexington, KY, USA
- Hematology-Oncology Department, Faculty of Medicine, Saint Joseph University of Beirut, Beirut, Lebanon
- Medical Oncology, IRCCS, National Cancer Institute Regina Elena, Rome, Italy
- Clinical Oncology, Sociedad de Oncología y Hematología del Cesar, Valledupar, Colombia
- Department of Medical Oncology, Army Hospital Research and Referral, New Delhi, India
- Instituto Nacional de Ciencias Médicas y Nutrición Salvador Zubirán, Mexico City, Mexico
- UOC Oncologia A, Department of Hematology, Oncology and Dermatology, Policlinico Umberto I University Hospital, Sapienza University of Rome, Italy
- Department of Experimental Medicine, Sapienza University of Rome, Rome, Italy
- Medical Oncology, IRCCS Azienda Ospedaliero-Universitaria di Bologna, Bologna, Italy
- Department of Medical and Surgical Science (DIMEC), University of Bologna, Bologna, Italy
- Hospital Israelita Albert Einstein, São Paulo, SP, Brazil
- Oncology Unit, Macerata Hospital, Macerata, Italy
- General Director AST3 Macerata, Italy
- National Cancer Centre Singapore, Singapore, Singapore
- 2nd Propaedeutic Department of Internal Medicine, ATTIKON University Hospital, School of Medicine, National and Kapodistrian University of Athens, Athens, Greece
- Interdisciplinary Department of Medicine, University of Bari "Aldo Moro" and Division of Medical Oncology, AOU Consorziale Policlinico di Bari, Bari, Italy