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

IF 4.4 3区医学 Q2 ONCOLOGY

Targeted Oncology Pub Date : 2024-09-17 DOI:10.1007/s11523-024-01096-3

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

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引用次数: 0

Abstract

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.

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晚期肾细胞癌患者对一线免疫疗法联合用药的真实世界原发性耐药性（ARON-1）

背景基于免疫肿瘤联合疗法的治疗进展彻底改变了肾细胞癌患者的治疗。方法本研究收集了来自 22 个国家 72 个中心（1709 名患者）的数据，涉及年龄≥18 岁的转移性透明细胞肾细胞癌患者。所有患者均接受了一线免疫肿瘤联合治疗。数据包括患者人口统计学、组织学、转移部位和治疗反应。放射学评估遵循《实体瘤反应评估标准》1.1版。统计分析采用了 Kaplan-Meier 法、Cox 比例危险模型、逻辑回归和接收器操作特征曲线。Nivolumab/ipilimumab的预后率最高（27%），而pembrolizumab/lenvatinib的预后率最低（10%）。与非预后患者（55.7 个月）相比，原发性预后患者的中位总生存期（7.6 个月）明显较低，p < 0.001。在多变量分析中，肾切除术、肉瘤样去分化、中度/低度国际转移性 RCC 数据库联盟风险、骨转移和脑转移成为肾细胞癌原发患者总生存期的重要预测因素。逻辑回归显示，肝转移、中度/差国际转移性RCC数据库联盟风险、未手术与Pref风险增加之间存在显著关系。结论ARON-1研究为Pref患者提供了宝贵的见解，强调了这一早发耐药亚组所面临的挑战。已确定的预测因素可指导风险分层，帮助临床医生采取有针对性的治疗方法。

本文章由计算机程序翻译，如有差异，请以英文原文为准。

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来源期刊

Targeted Oncology 医学-肿瘤学

CiteScore

8.40

自引率

3.70%

发文量

审稿时长

>12 weeks

期刊介绍： Targeted Oncology addresses physicians and scientists committed to oncology and cancer research by providing a programme of articles on molecularly targeted pharmacotherapy in oncology. The journal includes: Original Research Articles on all aspects of molecularly targeted agents for the treatment of cancer, including immune checkpoint inhibitors and related approaches. Comprehensive narrative Review Articles and shorter Leading Articles discussing relevant clinically established as well as emerging agents and pathways. Current Opinion articles that place interesting areas in perspective. Therapy in Practice articles that provide a guide to the optimum management of a condition and highlight practical, clinically relevant considerations and recommendations. Systematic Reviews that use explicit, systematic methods as outlined by the PRISMA statement. Adis Drug Reviews of the properties and place in therapy of both newer and established targeted drugs in oncology.