一线免疫检查点抑制剂治疗晚期非透明细胞肾细胞癌患者的结局。
Outcomes of patients with advanced non-clear cell renal cell carcinoma treated with first-line immune checkpoint inhibitor therapy.
机构信息
University of Manitoba, Winnipeg, MB, Canada; CancerCare Manitoba Research Institute, CancerCare Manitoba, Winnipeg, MB, Canada.
Queen's University, Kingston, ON, Canada.
出版信息
Eur J Cancer. 2022 Aug;171:124-132. doi: 10.1016/j.ejca.2022.05.002. Epub 2022 Jun 16.
BACKGROUND
Immune checkpoint inhibitors (ICI) have demonstrated impressive activity in metastatic clear-cell renal cell carcinoma (ccRCC) and have become standard treatment options for patients with advanced disease. Data supporting the effectiveness of ICI-based therapy in advanced non-clear cell RCC (nccRCC) is more limited.
METHODS
We performed a retrospective analysis using the International Metastatic RCC Database Consortium (IMDC) to evaluate the outcomes of patients with advanced nccRCC. Patients were classified into three groups based on first-line therapy: ICI-based therapy (monotherapy or combination), vascular endothelial growth factor (VEGF) inhibitor monotherapy, or mammalian target of rapamycin (mTOR) inhibitor monotherapy. The primary outcome was overall survival (OS). Secondary outcomes were time to treatment failure (TTF) and objective response rate (ORR). We used the Kaplan-Meier method to compare OS and TTF between treatment groups and Cox proportional hazards models to adjust for prognostic covariates.
RESULTS
We identified a total of 1145 patients with metastatic nccRCC. The most common subtype was papillary RCC (54.9%). For first-line therapy, 74.3% received VEGF monotherapy, 15% received mTOR monotherapy, and 10.7% received ICI-based therapy. Median OS in the ICI group was 28.6 months, versus 16.4 months in the VEGF group and 12.2 months in the mTOR group. Median TTF in the ICI group was 6.9 months, versus 5.0 months in the VEGF group and 3.9 months in the mTOR group. ORR was 27.2% in the ICI group, 14.5% in the VEGF group, and 9% in the mTOR group. After adjusting for the IMDC risk group, histological subtype, and age, the hazard ratio for OS was 0.57 (95% CI 0.42-0.78, p < 0.0001) for ICI versus VEGF and 0.50 (95% CI 0.36-0.71, p < 0.0001) for ICI versus mTOR.
CONCLUSIONS
In advanced nccRCC, first-line ICI-based treatment appears to be associated with improved OS compared to VEGF and mTOR targeted therapy. These results should be confirmed in prospective randomised trials.
背景
免疫检查点抑制剂（ICI）在转移性透明细胞肾细胞癌（ccRCC）中显示出令人印象深刻的疗效，已成为晚期疾病患者的标准治疗选择。支持 ICI 为基础的治疗在晚期非透明细胞肾细胞癌（nccRCC）中有效的数据更为有限。
方法
我们使用国际转移性肾细胞癌数据库联盟（IMDC）进行了回顾性分析，以评估晚期 nccRCC 患者的结局。根据一线治疗将患者分为三组：ICI 为基础的治疗（单药或联合）、血管内皮生长因子（VEGF）抑制剂单药或哺乳动物雷帕霉素靶蛋白（mTOR）抑制剂单药。主要结局是总生存期（OS）。次要结局是治疗失败时间（TTF）和客观缓解率（ORR）。我们使用 Kaplan-Meier 方法比较治疗组之间的 OS 和 TTF，并使用 Cox 比例风险模型调整预后协变量。
结果
我们共确定了 1145 例转移性 nccRCC 患者。最常见的亚型是乳头状 RCC（54.9%）。对于一线治疗，74.3%接受 VEGF 单药治疗，15%接受 mTOR 单药治疗，10.7%接受 ICI 为基础的治疗。ICI 组的中位 OS 为 28.6 个月，VEGF 组为 16.4 个月，mTOR 组为 12.2 个月。ICI 组的中位 TTF 为 6.9 个月，VEGF 组为 5.0 个月，mTOR 组为 3.9 个月。ICI 组的 ORR 为 27.2%，VEGF 组为 14.5%，mTOR 组为 9%。在调整 IMDC 风险组、组织学亚型和年龄后，ICI 与 VEGF 相比，OS 的风险比为 0.57（95%CI 0.42-0.78，p<0.0001），ICI 与 mTOR 相比，OS 的风险比为 0.50（95%CI 0.36-0.71，p<0.0001）。
结论
在晚期 nccRCC 中，与 VEGF 和 mTOR 靶向治疗相比，一线 ICI 为基础的治疗似乎与改善 OS 相关。这些结果应在前瞻性随机试验中得到证实。
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