Therapeutic advancements based on immuno-oncology combinations have revolutionized the management of patients with renal cell carcinoma. However, patients who have progressive disease as the best response, "primary refractory" (Pref), face dismal outcomes.
Our multicenter retrospective real-world study aims to assess the prevalence and clinicopathological characteristics of Pref patients.
This study collected data from 72 centers across 22 countries (1709 patients), involving patients aged ≥18 years with metastatic clear cell renal cell carcinoma. All patients were treated with first-line immune-oncology combinations. Data included patient demographics, histology, metastatic sites, and treatment responses. Radiological assessments followed Response Evaluation Criteria in Solid Tumors version 1.1. Statistical analyses employed Kaplan-Meier method, Cox proportional hazard models, logistic regression, and the receiver operating characteristic curve.
In our study, the Pref rate was 19%. Nivolumab/ipilimumab showed the highest Pref rate (27%), while pembrolizumab/lenvatinib exhibited the lowest (10%). Primary refactory patients demonstrated significantly lower median overall survival (7.6 months) compared with non-Pref patients (55.7 months), p < 0.001. At the multivariate analysis, nephrectomy, sarcomatoid de-differentiation, intermediate/poor International Metastatic RCC Database Consortium risk, and bone and brain metastases emerged as significant predictors of overall survival for Pref patients with renal cell carcinoma. Logistic regression showed a significant relationship between liver metastases, intermediate/poor International Metastatic RCC Database Consortium risk, and no surgery and an increased risk of Pref. This study presents limitations, mainly because of its retrospective design.
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.
Targeted oncology. 2024 Sep 17 [Epub ahead of print]
Daniele Santini, Haoran Li, Giandomenico Roviello, Se Hoon Park, Enrique Grande, Jakub Kucharz, Umberto Basso, Ondrej Fiala, Fernando Sabino Marques Monteiro, Alexandr Poprach, Sebastiano Buti, Javier Molina-Cerrillo, Martina Catalano, Tomas Buchler, Emmanuel Seront, Jawaher Ansari, Zin W Myint, Marwan Ghosn, Fabio Calabrò, Ray Manneh Kopp, Dipen Bhuva, Maria T Bourlon, Michela Roberto, Mattia Alberto Di Civita, Veronica Mollica, Andrea Marchetti, Andrey Soares, Nicola Battelli, Marco Ricci, Ravindran Kanesvaran, Aristotelis Bamias, Camillo Porta, Francesco Massari, Matteo Santoni
Department of Radiological, Oncological and Pathological Sciences, Policlinico Umberto I, University of Rome, 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, University Hospital in Pilsen, Charles University, Pilsen, Czech Republic., Latin American Cooperative Oncology Group - LACOG, Porto Alegre, Brazil., Masaryk Memorial Cancer Institute, Brno, Czech Republic., Department of Medicine and Surgery, University of Parma - Oncology Unit, University Hospital of Parma, 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., Department of Hematology, Oncology and Dermatology, UOC Oncologia A, Policlinico Umberto I University Hospital, Sapienza University of Rome, Rome, Italy., Medical Oncology, IRCCS Azienda Ospedaliero-Universitaria di Bologna, Bologna, Italy., Oncology Unit, Macerata Hospital, Macerata, Italy., General Director AST3, Macerata, Italy., National Cancer Centre Singapore, Singapore, Singapore., 2nd Propaedeutic Department of Internal Medicine, School of Medicine, ATTIKON University Hospital, National and Kapodistrian University of Athens, Athens, Greece., Interdisciplinary Department of Medicine, Division of Medical Oncology, University of Bari "Aldo Moro", AOU Consorziale Policlinico di Bari, Bari, Italy., Medical Oncology, IRCCS Azienda Ospedaliero-Universitaria di Bologna, Bologna, Italy. .
PubMed http://www.ncbi.nlm.nih.gov/pubmed/39289313