Department of Oncology, Karmanos Cancer Institute/Wayne State University, 4 HWCRC 4100 John R, Detroit, MI, 48201, USA.
Biostatistics Core, Karmanos Cancer Institute, Department of Oncology, School of Medicine, Wayne State University, Detroit, MI, USA.
J Immunother Cancer. 2017 Oct 17;5(1):82. doi: 10.1186/s40425-017-0287-5.
There is an unmet need to determine factors predictive of clinical benefit, to guide therapeutic sequencing and selection in metastatic RCC (mRCC). We evaluated clinical factors such as the neutrophil lymphocyte ratio (NLR) and duration of prior anti-vascular endothelial growth factor (VEGF) inhibitors, as predictors of response rate, progression free survival (PFS) and overall survival (OS) in mRCC patients treated with immune checkpoint inhibitor (ICI).
Regulatory approval was obtained. A single center retrospective chart review of mRCC patients at Karmanos Cancer Institute, treated with ICI based therapy (PD-1/PD-L1 inhibitors) was conducted. Data were collected on demographics, smoking status, prognostic scoring (Memorial Sloan Kettering and Heng criteria), NLR pretherapy, post 1 and 4 doses of ICI, and duration of prior anti-VEGF therapy ≥6 months or <6.
42 patients were evaluated with median age of 61 years (range, 24-85). Pretherapy NLR < 3 and ≥3 was seen in 19 (45%) and 23 (55%) patients, respectively. 24 (57%) and 18 (43%) patients had prior anti-VEGF inhibitors for a duration of ≥6 months and <6 months, respectively. 12 (29%), 22 (52%) and 8 (19%) patients had favorable, intermediate and poor risk disease based on Heng criteria, respectively. Multivariable analysis showed pretherapy NLR ≥3 was predictive of shorter PFS and OS when treated with ICI with median 3.08 months and 13.50 months, respectively, versus 15.57 months and not reached for NLR < 3 (adjusted p-values =0.003 and 0.025, respectively). Prior anti-VEGF therapy <6 months was predictive of increased likelihood of benefit from ICI therapies (adjusted p = 0.028). The median PFS was 3.72 months and 14.33 months, respectively, in cases with prior anti-VEGF therapy for ≥6 months and <6 months.
Pretherapy NLR <3 and duration of prior anti-VEGF therapy of <6 months, are independent statistically significant predictors of longer PFS and OS with ICI therapy in mRCC. Validation is required in a larger sample size with multi-institutional collaboration.
需要确定预测临床获益的因素，以指导转移性肾细胞癌（mRCC）的治疗顺序和选择。我们评估了中性粒细胞与淋巴细胞比值（NLR）和先前接受抗血管内皮生长因子（VEGF）抑制剂治疗的时间等临床因素，以预测接受免疫检查点抑制剂（ICI）治疗的 mRCC 患者的反应率、无进展生存期（PFS）和总生存期（OS）。
获得监管部门批准。对 Karmanos Cancer Institute 接受基于 ICI 的治疗（PD-1/PD-L1 抑制剂）的 mRCC 患者进行了单中心回顾性图表审查。收集了人口统计学数据、吸烟状况、预后评分（Memorial Sloan Kettering 和 Heng 标准）、ICI 前的 NLR、ICI 后第 1 天和第 4 天的 NLR，以及先前接受抗 VEGF 治疗的时间≥6 个月或<6 个月。
42 例患者中位年龄为 61 岁（范围为 24-85 岁）。ICI 前 NLR<3 和≥3 的患者分别为 19 例（45%）和 23 例（55%）。分别有 24 例（57%）和 18 例（43%）患者的先前抗 VEGF 抑制剂治疗时间≥6 个月和<6 个月。根据 Heng 标准，分别有 12 例（29%）、22 例（52%）和 8 例（19%）患者患有有利、中等和不良风险疾病。多变量分析显示，ICI 治疗前 NLR≥3 与较短的 PFS 和 OS 相关，分别为 3.08 个月和 13.50 个月，而 NLR<3 的中位 PFS 和 OS 分别为 15.57 个月和未达到（调整后的 p 值分别为 0.003 和 0.025）。先前抗 VEGF 治疗<6 个月与 ICI 治疗获益的可能性增加相关（调整后的 p 值=0.028）。在先前接受抗 VEGF 治疗≥6 个月和<6 个月的患者中，中位 PFS 分别为 3.72 个月和 14.33 个月。
ICI 治疗前 NLR<3 和先前抗 VEGF 治疗时间<6 个月是 mRCC 患者 PFS 和 OS 延长的独立统计学显著预测因素。需要在更大的样本量和多机构合作中进行验证。
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