Real-World Primary Resistance to First-Line Immune-Based Combinations in Patients with Advanced Renal Cell Carcinoma (ARON-1)

期刊论文
发表日期：

2024年9月17日

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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

摘要

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” (P_ref), face dismal outcomes.

Objective

Our multicenter retrospective real-world study aims to assess the prevalence and clinicopathological characteristics of P_ref 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 P_ref rate was 19%. Nivolumab/ipilimumab showed the highest P_ref rate (27%), while pembrolizumab/lenvatinib exhibited the lowest (10%). Primary refactory patients demonstrated significantly lower median overall survival (7.6 months) compared with non-P_ref 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 P_ref 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 P_ref. This study presents limitations, mainly because of its retrospective design.

Conclusions

The ARON-1 study provides valuable insights into P_ref patients, emphasizing the challenges of this precociously resistant subgroup. Identified predictors could guide risk stratification, aiding clinicians in tailored therapeutic approaches.