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.
Target Oncol. 2024 Nov;19(6):893-903. doi: 10.1007/s11523-024-01096-3. Epub 2024 Sep 17.
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), face dismal outcomes.
Our multicenter retrospective real-world study aims to assess the prevalence and clinicopathological characteristics of P 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 P rate was 19%. Nivolumab/ipilimumab showed the highest P 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 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 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. This study presents limitations, mainly because of its retrospective design.
The ARON-1 study provides valuable insights into P patients, emphasizing the challenges of this precociously resistant subgroup. Identified predictors could guide risk stratification, aiding clinicians in tailored therapeutic approaches.
基于免疫肿瘤学联合治疗的进展彻底改变了肾细胞癌患者的治疗管理。然而，作为最佳反应的进展性疾病患者，即“原发性难治性”（P）患者，预后较差。
我们的多中心回顾性真实世界研究旨在评估 P 患者的患病率和临床病理特征。
本研究从 22 个国家的 72 个中心收集数据（1709 例患者），纳入年龄≥18 岁的转移性透明细胞肾细胞癌患者。所有患者均接受一线免疫肿瘤学联合治疗。数据包括患者人口统计学、组织学、转移部位和治疗反应。采用实体瘤反应评价标准 1.1 进行影像学评估。统计分析采用 Kaplan-Meier 法、Cox 比例风险模型、逻辑回归和受试者工作特征曲线。
在本研究中，P 发生率为 19%。纳武利尤单抗/伊匹单抗显示的 P 发生率最高（27%），而帕博利珠单抗/仑伐替尼则最低（10%）。原发性难治性患者的中位总生存期明显低于非 P 患者（7.6 个月对 55.7 个月），p<0.001。多变量分析显示，肾切除术、肉瘤样去分化、中/高危国际转移性肾细胞癌数据库联盟风险以及骨和脑转移是 P 患者肾细胞癌总生存期的显著预测因素。逻辑回归显示肝转移、中/高危国际转移性肾细胞癌数据库联盟风险和未行手术与 P 风险增加之间存在显著关系。本研究存在一定局限性，主要是因为其回顾性设计。
ARON-1 研究为 P 患者提供了有价值的见解，强调了这一早期耐药亚组所面临的挑战。确定的预测因素可以指导风险分层，帮助临床医生制定个体化的治疗方法。
