Department of Genitourinary Oncology, Moffitt Cancer Center, Tampa, Florida, USA.
The University of Texas MD Anderson Cancer Center, Houston, Texas, USA.
Oncologist. 2020 Mar;25(3):252-258. doi: 10.1634/theoncologist.2019-0372. Epub 2019 Sep 9.
Nivolumab alone and in combination with ipilimumab is approved for the treatment of patients with metastatic renal cell carcinoma (RCC) who received prior vascular endothelial growth factor receptor tyrosine kinase inhibitors (VEGFR-TKI) and those who are treatment naive, respectively. However, the clinical activity of nivolumab in non-clear cell RCC (nccRCC) is unknown, as these patients were excluded from the trials.
We reviewed the records of patients who received nivolumab for nccRCC and ccRCC with >20% rhabdoid with the primary endpoint to assess the objective response rate (ORR). We assessed radiographic response using RECIST, v1.1. Secondary endpoints were progression-free survival (PFS) and overall survival (OS). We also reviewed the literature to identify studies reporting on the clinical activity of immune checkpoint inhibitors in nccRCC, and performed a meta-analysis of proportions for ORR and disease control rate (DCR).
Twelve patients (30%) had papillary histology, 11 (27.5%) had unclassified, 8 (20%) had ccRCC with rhabdoid component, 5 (12.5%) had chromophobe, 3 (7.5%) had translocation, and 1 (2.5%) had mucinous tubular and spindle cell carcinoma. Overall, seven patients (21.6%, 95% confidence interval [CI], 8.7%-37.9%) had an objective response, including three patients (8.8%, 95% confidence interval [CI], 1.9%-23.7%) who achieved a complete remission. At a median follow-up of 24.5 monoths (95% CI, 17.7-32.6), median PFS was 4.9 monoths (95% CI, 3.53-10.27) and median OS was 21.7 monoths (95% CI, 7.83 mo to not reached). There were no treatment-related deaths. We also identified two retrospective studies reporting best ORR in patients with nccRCC receiving PD-1/PD-L1 checkpoint blockade. The ORR and DCR for the total cohort were, respectively, 18.6% (95% CI, 11.9%-26.4%) and 53.4% (95% CI, 44.2%-62.5%).
Nivolumab demonstrated activity in unclassified nccRCC and ccRCC with >20% rhabdoid; further randomized clinical trials are warranted.
This article reports on the clinical activity and safety of immune checkpoint inhibitors in non-clear cell kidney cancer. The retrospective data with the meta-analysis provides a summary that will help guide the treatment of this rare and heterogeneous group of kidney cancers.
纳武利尤单抗单药及联合伊匹单抗获批用于治疗接受过血管内皮生长因子受体酪氨酸激酶抑制剂（VEGFR-TKI）治疗的转移性肾细胞癌（RCC）患者和治疗初治患者。然而，纳武利尤单抗在非透明细胞肾细胞癌（nccRCC）中的临床活性尚不清楚，因为这些患者被排除在临床试验之外。
我们回顾了接受纳武利尤单抗治疗 nccRCC 和 ccRCC 伴>20%横纹肌样变患者的病历，主要终点是评估客观缓解率（ORR）。我们使用 RECIST v1.1 评估影像学反应。次要终点是无进展生存期（PFS）和总生存期（OS）。我们还查阅了文献，以确定报告免疫检查点抑制剂在 nccRCC 中临床活性的研究，并对 ORR 和疾病控制率（DCR）进行了比例的荟萃分析。
12 名患者（30%）为乳头状组织学，11 名（27.5%）为未分类，8 名（20%）为伴>20%横纹肌样变的 ccRCC，5 名（12.5%）为嫌色细胞癌，3 名（7.5%）为易位性，1 名（2.5%）为黏液性管状和梭形细胞癌。总体而言，7 名患者（21.6%，95%置信区间[CI]，8.7%-37.9%）有客观缓解，包括 3 名患者（8.8%，95%CI，1.9%-23.7%）达到完全缓解。在中位随访 24.5 个月（95%CI，17.7-32.6）时，中位 PFS 为 4.9 个月（95%CI，3.53-10.27），中位 OS 为 21.7 个月（95%CI，7.83 个月至未达到）。无治疗相关死亡。我们还确定了两项回顾性研究，报告了 PD-1/PD-L1 检查点阻断治疗 nccRCC 患者的最佳 ORR。总队列的 ORR 和 DCR 分别为 18.6%（95%CI，11.9%-26.4%）和 53.4%（95%CI，44.2%-62.5%）。
纳武利尤单抗在未分类的 nccRCC 和>20%横纹肌样变的 ccRCC 中显示出活性；需要进一步的随机临床试验。
本文报告了免疫检查点抑制剂在非透明细胞肾癌中的临床活性和安全性。回顾性数据和荟萃分析提供了一个总结，将有助于指导治疗这一罕见且异质性的肾癌群体。
