Oncology Unit, Macerata Hospital, Macerata, Italy.
Medical Oncology Unit, University Hospital of Parma - Department of Medicine and Surgery, University of Parma, Parma, Italy.
Eur Urol Oncol. 2024 Feb;7(1):102-111. doi: 10.1016/j.euo.2023.07.003. Epub 2023 Jul 21.
Renal c carcinoma (RCC) is one of the most common urinary cancers worldwide, with a predicted increase in incidence in the coming years. Immunotherapy, as a single agent, in doublets, or in combination with anti-vascular endothelial growth factor receptor tyrosine kinase inhibitors (TKIs), has rapidly become a cornerstone of the RCC therapeutic scenario, but no head-to-head comparisons have been made. In this setting, real-world evidence emerges as a cornerstone to guide clinical decisions.
The objective of this retrospective study was to assess the outcome of patients treated with first-line immune combinations or immune oncology (IO)-TKIs for advanced RCC.
DESIGN, SETTING, AND PARTICIPANTS: Data from 930 patients, 654 intermediate risk and 276 poor risk, were collected retrospectively from 58 centers in 20 countries. Special data such as sarcomatoid differentiation, body mass index, prior nephrectomy, and metastatic localization, in addition to biochemical data such as hemoglobin, platelets, calcium, lactate dehydrogenase, neutrophils, and radiological response by investigator's criteria, were collected.
Overall survival (OS) and progression-free survival (PFS) were estimated using the Kaplan-Meier method. The median follow-up was calculated by the inverse Kaplan-Meier method.
The median follow-up time was 18.7 mo. In the 654 intermediate-risk patients, the median OS and PFS were significantly longer in patients with the intermediate than in those with the poor International Metastatic Renal Cell Carcinoma Database Consortium (IMDC) criteria (38.9 vs 17.3 mo, 95% confidence interval [CI] p < 0.001, and 17.3 vs 11.6 mo, 95% CI p < 0.001, respectively). In the intermediate-risk subgroup, the OS was 55.7 mo (95% CI 31.4-55.7) and 40.2 mo (95% CI 29.6-51.6) in patients treated with IO + TKI and IO + IO combinations, respectively (p = 0.047). PFS was 30.7 mo (95% CI 16.5-55.7) and 13.2 mo (95% CI 29.6-51.6) in intermediate-risk patients treated with IO + TKI and IO + IO combinations, respectively (p < 0.001). In the poor-risk subgroup, the median OS and PFS did not show a statistically significant difference between IO + IO and IO + TKI. Our study presents several limitations, mainly due to its retrospective nature.
Our results showed differences between the IO + TKI and IO + IO combinations in intermediate-risk patients. A clear association with longer PFS and OS in favor of patients who received the IO + TKI combinations compared with the IO-IO combination was observed. Instead, in the poor-risk group, we observed no significant difference in PFS or OS between patients who received different combinations.
Renal cancer is one of the most frequent genitourinary tumors. Treatment is currently based on immunotherapy combinations or immunotherapy with tyrosine kinase inhibitors, but there are no comparisons between these.In this study, we have analyzed the clinical course of 930 patients from 58 centers in 20 countries around the world. We aimed to analyze the differences between the two main treatment strategies, combination of two immunotherapies versus immunotherapy + antiangiogenic therapy, and found in real-life data that intermediate-risk patients (approximately 60% of patients with metastatic renal cancer) seem to benefit more from the combination of immunotherapy + antiangiogenic therapy than from double immunotherapy. No such differences were found in poor-risk patients. This may have important implications in daily practice decision-making for these patients.
肾细胞癌（RCC）是全球最常见的泌尿系统癌症之一，预计未来几年发病率将会上升。免疫疗法作为单一药物、双药联合或与抗血管内皮生长因子受体酪氨酸激酶抑制剂（TKIs）联合应用，已迅速成为 RCC 治疗方案的基石，但尚未进行头对头比较。在这种情况下，真实世界的证据成为指导临床决策的基石。
本回顾性研究旨在评估晚期 RCC 患者接受一线免疫联合治疗或免疫肿瘤学（IO）-TKIs 治疗的结果。
设计、地点和参与者：从 20 个国家的 58 个中心回顾性收集了 930 名患者的数据，其中 654 名患者为中危风险，276 名患者为高危风险。除了生化数据（如血红蛋白、血小板、钙、乳酸脱氢酶、中性粒细胞和研究者标准的放射学反应）外，还收集了肉瘤样分化、体重指数、肾切除术和转移部位等特殊数据。
使用 Kaplan-Meier 法估计总生存期（OS）和无进展生存期（PFS）。通过反向 Kaplan-Meier 法计算中位随访时间。
中位随访时间为 18.7 个月。在 654 名中危风险患者中，与低危国际转移性肾细胞癌数据库联盟（IMDC）标准患者相比，中危患者的 OS 和 PFS 明显更长（38.9 与 17.3 个月，95%置信区间[CI]p<0.001；17.3 与 11.6 个月，95%CI p<0.001）。在中危亚组中，IO+TKI 和 IO+IO 联合治疗的患者 OS 分别为 55.7 个月（95%CI 31.4-55.7）和 40.2 个月（95%CI 29.6-51.6）（p=0.047）。PFS 分别为 30.7 个月（95%CI 16.5-55.7）和 13.2 个月（95%CI 29.6-51.6）（p<0.001）。在高危亚组中，IO+IO 和 IO+TKI 治疗的患者 OS 和 PFS 之间无统计学显著差异。本研究存在一些局限性，主要是由于其回顾性性质。
我们的结果显示，在中危风险患者中，IO+TKI 和 IO+IO 联合治疗之间存在差异。与 IO-IO 联合治疗相比，IO+TKI 联合治疗的患者具有更长的 PFS 和 OS，这一结果具有显著意义。相比之下，在高危组中，我们观察到接受不同联合治疗的患者的 PFS 或 OS 之间没有显著差异。
肾细胞癌是泌尿系统最常见的肿瘤之一。目前的治疗方法基于免疫治疗联合或免疫治疗联合酪氨酸激酶抑制剂，但这些治疗方法之间没有比较。在这项研究中，我们分析了来自全球 20 个国家 58 个中心的 930 名患者的临床病程。我们旨在分析两种主要治疗策略（两种免疫疗法联合与免疫治疗加抗血管生成治疗）之间的差异，并在真实世界数据中发现，中危风险患者（约 60%的转移性肾细胞癌患者）似乎从免疫治疗加抗血管生成治疗联合治疗中获益更多，而不是从双重免疫治疗中获益更多。在高危风险患者中没有发现这种差异。这可能对这些患者的日常实践决策具有重要意义。
