TY - JOUR
T1 - Real-World Primary Resistance to First-Line Immune-Based Combinations in Patients with Advanced Renal Cell Carcinoma (ARON-1)
AU - Santini, Daniele
AU - Li, Haoran
AU - Roviello, Giandomenico
AU - Park, Se Hoon
AU - Grande, Enrique
AU - Kucharz, Jakub
AU - Basso, Umberto
AU - Fiala, Ondrej
AU - Monteiro, Fernando Sabino Marques
AU - Poprach, Alexandr
AU - Buti, Sebastiano
AU - Molina-Cerrillo, Javier
AU - Catalano, Martina
AU - Buchler, Tomas
AU - Seront, Emmanuel
AU - Ansari, Jawaher
AU - Myint, Zin W.
AU - Ghosn, Marwan
AU - Calabrò, Fabio
AU - Kopp, Ray Manneh
AU - Bhuva, Dipen
AU - Bourlon, Maria T.
AU - Roberto, Michela
AU - Di Civita, Mattia Alberto
AU - Mollica, Veronica
AU - Marchetti, Andrea
AU - Soares, Andrey
AU - Battelli, Nicola
AU - Ricci, Marco
AU - Kanesvaran, Ravindran
AU - Bamias, Aristotelis
AU - Porta, Camillo
AU - Massari, Francesco
AU - Santoni, Matteo
N1 - Publisher Copyright:
© The Author(s), under exclusive licence to Springer Nature Switzerland AG 2024.
PY - 2024/11
Y1 - 2024/11
N2 - Background: 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. 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 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. Results: 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. 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.
AB - Background: 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. 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 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. Results: 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. 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.
UR - https://www.scopus.com/pages/publications/85204300144
U2 - 10.1007/s11523-024-01096-3
DO - 10.1007/s11523-024-01096-3
M3 - Article
C2 - 39289313
AN - SCOPUS:85204300144
SN - 1776-2596
VL - 19
SP - 893
EP - 903
JO - Targeted Oncology
JF - Targeted Oncology
IS - 6
ER -
SDG 3 Good Health and Well-being