Department of Thoracic/Head and Neck Medical Oncology, The University of Texas MD Anderson Cancer Center, Houston, Texas; Department of Oncology, Nanjing First Hospital, Nanjing Medical University, Nanjing, People's Republic of China.
Department of Thoracic/Head and Neck Medical Oncology, The University of Texas MD Anderson Cancer Center, Houston, Texas.
J Thorac Oncol. 2020 Sep;15(9):1449-1459. doi: 10.1016/j.jtho.2020.04.026. Epub 2020 May 8.
Programmed death-ligand 1 (PD-L1) expression may vary in different disease sites and at different time points of the disease course. We aimed to investigate PD-L1 heterogeneity and its usefulness as a predictive value for immune checkpoint inhibitor (ICI) therapy in patients with NSCLC.
PD-L1 expression was analyzed in 1398 patients with NSCLC. The predictive value of PD-L1 for ICIs in 398 patients with metastatic NSCLC was assessed.
PD-L1 was significantly associated with biopsy sites (p = 0.004). Adrenal, liver, and lymph node (LN) metastases had the highest PD-L1 expression as a continuous variable and at 1% or 50% cutoff. PD-L1 expression was lower in bone and brain metastases. Among 112 patients with two specimens tested, 55 (49%) had major changes in PD-L1 falling into different clinically relevant categories (<1%, 1%-49%, ≥50%) at different time points. Previous ICI therapy was associated with significant decrease in PD-L1 compared with treatment-naive counterparts (p = 0.015). Patients with metastatic NSCLC treated with ICI (n = 398) were divided into three cohorts on the basis of biopsy sites: lung (n = 252), LN (n = 85), and distant metastasis (n = 61). Higher PD-L1 in lung or distant metastasis specimens was associated with higher response rate, longer progression-free survival, and overall survival. However, PD-L1 in LN biopsies was not associated with either response or survival.
PD-L1 varies substantially across different anatomical sites and changes during the clinical course. PD-L1 from different biopsy sites may have different predictive values for benefit from ICIs in NSCLC.
程序性死亡配体 1（PD-L1）的表达可能在不同的疾病部位和疾病过程的不同时间点有所不同。我们旨在研究 PD-L1 的异质性及其作为非小细胞肺癌（NSCLC）患者免疫检查点抑制剂（ICI）治疗预测价值的作用。
对 1398 例 NSCLC 患者进行 PD-L1 表达分析。评估 398 例转移性 NSCLC 患者的 PD-L1 对 ICI 的预测价值。
PD-L1 与活检部位显著相关（p=0.004）。肾上腺、肝脏和淋巴结（LN）转移作为连续变量和 1%或 50%截断值时，PD-L1 表达最高。骨和脑转移的 PD-L1 表达较低。在 112 例接受两种标本检测的患者中，55 例（49%）在不同时间点的不同临床相关类别（<1%、1%-49%、≥50%）中 PD-L1 发生主要变化。与治疗初治患者相比，接受过 ICI 治疗的患者 PD-L1 显著下降（p=0.015）。根据活检部位将接受 ICI 治疗的转移性 NSCLC 患者（n=398）分为三组：肺（n=252）、LN（n=85）和远处转移（n=61）。肺或远处转移标本中 PD-L1 水平较高与更高的反应率、更长的无进展生存期和总生存期相关。然而，LN 活检中的 PD-L1 与反应或生存无关。
PD-L1 在不同解剖部位差异较大，在临床过程中发生变化。来自不同活检部位的 PD-L1 可能对 NSCLC 患者从 ICI 中获益具有不同的预测价值。
