Taussig Cancer Institute, Cleveland Clinic, Cleveland, OH, USA.
Department of Quantitative Health Sciences, Lerner Research Institute, Cleveland Clinic, Cleveland, OH, USA.
J Immunother Cancer. 2018 Oct 17;6(1):107. doi: 10.1186/s40425-018-0425-8.
Nivolumab is approved for the treatment of refractory metastatic renal cell carcinoma. Patterns and predictors of progressive disease (PD) on nivolumab, and outcomes in such patients are lacking.
A retrospective analysis of patients (pts) with metastatic clear cell renal cell carcinoma (ccRCC) who received nivolumab at Cleveland Clinic (2015-2017) was performed. PD was defined per Response Evaluation Criteria in Solid Tumors (RECIST) v1.1 or clinical progression as per treating physician. Univariate analyses (UVA) and multivariate analyses (MVA) were used to identify clinical and laboratory markers as potential predictors of progression-free survival (PFS).
Ninety patients with mean age of 65, 74% men, and 83% good or intermediate International Metastatic Renal Cell Carcinoma Database Consortium (IMDC) risk group were included. Median number of prior systemic treatments was 2 (range, 1-6). Median overall survival (OS) and PFS were 15.8 and 4.4 months, respectively. Fifty-seven patients (63%) had PD and 44% of patients with radiographic PD had new organ sites of metastases with brain (8/23, 35%) being the most common. Twelve patients received treatment beyond progression (TBP), and among 6 patients with available data, 3 (50%) had any tumor shrinkage (2 pts. with 17% shrinkage, one pt. with 29% shrinkage). Of 57 patients with PD, 28 patients (49%) were able to initiate subsequent treatment, mainly with axitinib and cabozantinib, while 40% of patients were transitioned to hospice after PD. In MVA, a higher baseline Neutrophil-to-Lymphocyte ratio (NLR) (HR, 1.86; 95% CI, 1.05-3.29; p = 0.033) was associated with an increased risk of progression, whereas higher (> 0.1 k/uL) baseline eosinophil count was associated with a lower risk of progression (HR, 0.54; 95% CI, 0.30-0.98; p = 0.042).
Brain was the most common site of PD in patients treated with nivolumab, and only half of patients progressing on nivolumab were able to initiate subsequent treatment. The risk of PD increased with a higher baseline NLR and reduced with a higher baseline eosinophil count.
纳武利尤单抗获批用于治疗难治性转移性肾细胞癌。纳武利尤单抗治疗后出现疾病进展（PD）的模式和预测因素以及此类患者的结局尚不清楚。
对克利夫兰诊所（2015-2017 年）接受纳武利尤单抗治疗的转移性透明细胞肾细胞癌（ccRCC）患者进行回顾性分析。PD 按实体瘤反应评价标准（RECIST）v1.1 或根据治疗医生的临床进展定义。采用单因素分析（UVA）和多因素分析（MVA）确定无进展生存期（PFS）的潜在预测因素。
共纳入 90 例平均年龄 65 岁、74%为男性、83%为国际转移性肾细胞癌数据库联盟（IMDC）预后良好或中等风险的患者。中位治疗线数为 2 条（范围 1-6 条）。中位总生存期（OS）和 PFS 分别为 15.8 个月和 4.4 个月。57 例（63%）患者出现 PD，44%影像学 PD 的患者有新的器官转移灶，其中脑部（8/23，35%）最常见。12 例患者在疾病进展后接受了治疗（TBP），6 例有可用数据的患者中，3 例（50%）有任何肿瘤缩小（2 例缩小 17%，1 例缩小 29%）。在 57 例 PD 患者中，28 例（49%）能够接受后续治疗，主要是阿昔替尼和卡博替尼，而 40%的患者在 PD 后转为临终关怀。在 MVA 中，较高的基线中性粒细胞与淋巴细胞比值（NLR）（HR，1.86；95%CI，1.05-3.29；p=0.033）与进展风险增加相关，而较高的（>0.1k/uL）基线嗜酸性粒细胞计数与进展风险降低相关（HR，0.54；95%CI，0.30-0.98；p=0.042）。
纳武利尤单抗治疗的患者中，脑部是 PD 最常见的部位，只有一半进展的患者能够接受后续治疗。PD 的风险随基线 NLR 的升高而增加，随基线嗜酸性粒细胞计数的升高而降低。
