Immune-based Combinations in Intermediate-/Poor-risk Patients with Non-clear Cell Renal Cell Carcinoma: Results from the ARON-1 Study.

IF 5.6 2区医学 Q1 UROLOGY & NEPHROLOGY

European urology focus Pub Date : 2025-07-29 DOI:10.1016/j.euf.2025.05.020

Francesco Massari, Veronica Mollica, Ray Manneh Kopp, Enrique Grande, Ondřej Fiala, Ravindran Kanesvaran, Haoran Li, Timothy J Schieber, Maria José Juan Fita, Alexandr Poprach, Cristian Lolli, Maria T Bourlon, Alfonso Gómez de Liaño, Francesco Grillone, Kaisa Sunela, Alessandro Rizzo, Marwan Ghosn, Linda Cerbone, Tarek Taha, Yüksel Ürün, Javier Molina-Cerrillo, Teresa Alonso-Gordoa, Edoardo Lenci, Inmaculada Orejana Martin, Hussam Abu-Sini, Pasquale Rescigno, Dipen Bhuva, Andre Poisl Fay, Vincenza Conteduca, Ahmet Yildirim, Matteo Rosellini, Umut Akova, Elisa Tassinari, Hatice Bölek, Andrey Soares, Fernando Sabino Marques Monteiro, Sebastiano Buti, Mehmet Asim Bilen, Matteo Santoni

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引用次数: 0

Abstract

Background and objective: Non-clear cell renal cell carcinoma (nccRCC) lacks direct comparisons of immune-based combinations, presenting an unmet need for defining optimal treatment for this specific population. This study aimed to assess the real-world efficacy of immune-based combinations in intermediate-/poor-risk nccRCC.

Methods: We conducted a multicenter, retrospective study of patients (≥18 yr) with metastatic nccRCC treated with first-line immune-based combinations across 56 centers in 17 countries between January 2021 and December 2024. Patients received pembrolizumab/lenvatinib, pembrolizumab/axitinib, nivolumab/cabozantinib, or nivolumab/ipilimumab. The primary endpoints were overall survival (OS) and progression-free survival (PFS), analyzed using Kaplan-Meier and Cox proportional-hazard models, and overall response rate (ORR) evaluated as per RECIST 1.1 criteria.

Key findings and limitations: Among the 323 patients analyzed (median follow-up: 21.2 mo), the median OS was 31.1 mo (95% confidence interval [CI] 24.6-40.4), with a 2-yr OS rate of 58%. The ORR was 38% (2% complete response and 36% partial response), and the median PFS was 13.0 mo (95% CI 10.0-17.4). Immune checkpoint inhibitors (ICIs) plus tyrosine kinase inhibitors (TKIs) significantly outperformed ICI doublets across efficacy metrics. Limitations include retrospective design and a selection bias.

Conclusions and clinical implications: Our analysis suggests ICI/TKI combinations as the optimal strategy for intermediate-/poor-risk nccRCC, with pembrolizumab/lenvatinib showing marked benefits. Further studies are needed to validate these findings.

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免疫联合治疗中/低危非透明细胞肾细胞癌：来自ARON-1研究的结果

背景和目的：非透明细胞肾细胞癌（nccRCC）缺乏基于免疫的联合治疗的直接比较，这表明对这一特定人群定义最佳治疗的需求尚未得到满足。本研究旨在评估基于免疫的联合治疗中/低风险nccRCC的实际疗效。方法：我们在2021年1月至2024年12月期间对17个国家56个中心接受一线免疫联合治疗的转移性nccRCC患者（≥18岁）进行了一项多中心回顾性研究。患者接受派姆单抗/lenvatinib、派姆单抗/axitinib、nivolumab/cabozantinib或nivolumab/ipilimumab治疗。主要终点是总生存期（OS）和无进展生存期（PFS），使用Kaplan-Meier和Cox比例风险模型进行分析，并根据RECIST 1.1标准评估总缓解率（ORR）。主要发现和局限性：在分析的323例患者中（中位随访：21.2个月），中位OS为31.1个月（95%可信区间[CI] 24.6-40.4）， 2年OS率为58%。ORR为38%（2%完全缓解和36%部分缓解），中位PFS为13.0个月（95% CI 10.0-17.4）。免疫检查点抑制剂（ICIs）加酪氨酸激酶抑制剂（TKIs）在疗效指标上明显优于ICI双药。局限性包括回顾性设计和选择偏差。结论和临床意义：我们的分析表明，ICI/TKI联合治疗是中/低风险nccRCC的最佳策略，派姆单抗/lenvatinib显示出明显的益处。需要进一步的研究来验证这些发现。

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来源期刊

European urology focus Medicine-Urology

CiteScore

10.40

自引率

3.70%

发文量

274

审稿时长

23 days

期刊介绍： European Urology Focus is a new sister journal to European Urology and an official publication of the European Association of Urology (EAU). EU Focus will publish original articles, opinion piece editorials and topical reviews on a wide range of urological issues such as oncology, functional urology, reconstructive urology, laparoscopy, robotic surgery, endourology, female urology, andrology, paediatric urology and sexual medicine. The editorial team welcome basic and translational research articles in the field of urological diseases. Authors may be solicited by the Editor directly. All submitted manuscripts will be peer-reviewed by a panel of experts before being considered for publication.