Medical Oncology Unit, Department of Systems Medicine, Tor Vergata University Hospital, Viale Oxford, 81, 00133, Rome, Italy.
Medical Oncology, Sarah Cannon Research Institute UK, London, UK.
Target Oncol. 2020 Jun;15(3):327-336. doi: 10.1007/s11523-020-00723-z.
Immune checkpoint inhibitors (ICIs) demonstrated improved overall survival (OS) in heavily pretreated unselected patients with metastatic gastro-esophageal junction (mGOJ)/gastric cancer (GC). Attempts to select patients based on programmed death-ligand 1 (PD-L1) expression appear to be suboptimal. A strong rationale suggests a prognostic role for inflammatory biomarkers for ICI-treated patients with mGOJ/GC.
Our objective was to assess whether inflammatory markers are associated with survival in ICI-treated patients with mGOJ/GC.
Ten inflammatory markers were retrospectively analyzed at baseline in 57 patients with mGOJ/GC with unknown PD-L1 status treated with second-line ICIs and correlated with OS. Selected variables were then analyzed in a multivariate Cox-regression model and used to build a GIPI nomogram.
Neutrophil/lymphocyte ratio (NLR) and C-reactive protein (CRP) as continuous variables and albumin categorized as less than versus greater than 30 g/dL were the most significant predictors of OS and were used to build the GIPI nomogram. Nomogram-based lowest, mid-low, mid-high, and highest risk quartiles were associated with median OS (mOS) of 14.9, 7.1, 5.6, and 2.1 months, respectively (hazard ratio [HR] of highest vs. lowest risk 4.94; p = 0.0002). By optimally dichotomizing CRP and NLR, patients with one or more of the risk factors NLR > 6, CRP > 15 mg/L, and albumin < 30 g/dL (n = 29) had an mOS of 3.9 versus 14.2 months for patients with no risk factor (n = 28) (HR 2.48; p = 0.0015).
GIPI, combining NLR, CRP, and albumin, is the first inflammatory index with a significant prognostic value in patients with mOGJ/GC receiving ICIs. GIPI merits validation in independent cohorts and prospective clinical trials.
免疫检查点抑制剂(ICIs)在未经选择的转移性胃食管交界处(mGOJ)/胃癌(GC)大量预处理患者中显示出改善的总生存期(OS)。基于程序性死亡配体 1(PD-L1)表达选择患者的尝试似乎并不理想。强有力的理由表明,对于接受 mGOJ/GC 的 ICI 治疗的患者,炎症生物标志物具有预后作用。
我们的目的是评估炎症标志物是否与接受 mGOJ/GC 的 ICI 治疗患者的生存相关。
回顾性分析了 57 例 mGOJ/GC 患者的基线时的 10 种炎症标志物,这些患者的 PD-L1 状态未知,接受二线 ICI 治疗,并与 OS 相关。然后在多变量 Cox 回归模型中分析选定的变量,并用于构建 GIPI 列线图。
中性粒细胞/淋巴细胞比值(NLR)和 C 反应蛋白(CRP)作为连续变量和白蛋白分类为小于或大于 30 g/dL 是 OS 的最显著预测因素,并用于构建 GIPI 列线图。基于列线图的最低、中低、中高和最高风险四分位数与中位 OS(mOS)分别为 14.9、7.1、5.6 和 2.1 个月相关(最高 vs. 最低风险的 HR 为 4.94;p=0.0002)。通过最佳地二分类 CRP 和 NLR,一个或多个危险因素 NLR>6、CRP>15mg/L 和白蛋白<30g/dL(n=29)的患者的 mOS 为 3.9 个月,而无危险因素(n=28)的患者 mOS 为 14.2 个月(HR 2.48;p=0.0015)。
GIPI,结合 NLR、CRP 和白蛋白,是第一个在接受 ICI 治疗的 mGOJ/GC 患者中具有显著预后价值的炎症指标。GIPI 需要在独立队列和前瞻性临床试验中进行验证。