Walker Paul R, Jayananda Sriraksha, Pasli Melisa, Muzaffar Mahvish
Division of Hematology/Oncology, Brody School of Medicine at East Carolina University, 600 Moye Blvd, Greenville, NC, 27834, USA.
Circulogene Theranostics, 3125 Independence Drive, Birmingham, AL, 35209, USA.
J Liq Biopsy. 2023 Dec 4;3:100130. doi: 10.1016/j.jlb.2023.100130. eCollection 2024 Mar.
Tissue programmed death ligand-1 (PD-L1) protein expression is associated with immune checkpoint inhibitor (ICI) treatment benefit in metastatic non-small cell lung cancer (NSCLC). However, tissue PD-L1 protein testing is limited by sampling tumor heterogeneity and fraught with tissue acquisition difficulties. A liquid biopsy-based PD-L1 assay could overcome these limitations of tissue PD-L1 testing.
An observational cohort of patients with metastatic NSCLC treated with first-line ICI-based therapies were retrospectively assessed for a pre-planned endpoint of median and 3-year landmark overall survival (OS) based upon plasma cell-free RNA (cfRNA) expression by a commercial exosome-free real-time qPCR assay or tissue PD-L1 protein expression (Dako 22C3) performed in CLIA/CAP accredited laboratories.
53 contemporaneous patients in 3 patient cohorts were compared with a median follow-up 34 months. 16 patients were cfRNA plasma positive, including 6 (37 %) tissue PD-L1 negative or tissue quantity not sufficient for testing; 16 were plasma PD-L1 negative but tissue PD-L1 positive; 21 were both plasma and tissue PD-L1 negative. OS was identical whether positive plasma cfRNA expression or positive tissue PD-L1 protein expression (median OS 15 months; 3-year landmark OS 30 %; hazard ratio (HR) 0.97; 95 % CI, 0.44-2.10; p-value = 0.93). Within the positive plasma PD-L1 cohort there was no differing OS whether tissue PD-L1 positive, negative, or unknown (median OS 15 months; 3-year landmark OS 30 %; HR 1.15; 95 % CI, 0.322-4.05; p-value = 0.81). Positive plasma cfRNA expression was associated with a numerically longer median and higher 3-year OS compared to patients lacking PD-L1 expression (median 15 months versus 8 months; 3-year landmark OS 30 % versus 15 %; HR 0.57, 95 % CI 0.26-1.20; p-value = 0.11).
In this retrospective study of real-world metastatic NSCLC patients, plasma cfRNA expression was similarly predictive of ICI benefit as tissue PD-L1 protein expression.
组织程序性死亡配体-1（PD-L1）蛋白表达与转移性非小细胞肺癌（NSCLC）的免疫检查点抑制剂（ICI）治疗获益相关。然而，组织PD-L1蛋白检测受肿瘤取样异质性限制，且获取组织困难重重。基于液体活检的PD-L1检测可克服组织PD-L1检测的这些局限性。
对接受一线ICI治疗的转移性NSCLC患者的观察性队列进行回顾性评估，根据商业无外泌体实时定量PCR检测的血浆游离RNA（cfRNA）表达或在CLIA/CAP认可实验室进行的组织PD-L1蛋白表达（Dako 22C3），评估预先设定的中位和3年标志性总生存期（OS）终点。
对3个患者队列中的53例同期患者进行比较，中位随访34个月。16例患者cfRNA血浆呈阳性，其中6例（37%）组织PD-L1阴性或组织量不足以进行检测；16例血浆PD-L1阴性但组织PD-L1阳性；21例血浆和组织PD-L1均为阴性。无论血浆cfRNA表达阳性还是组织PD-L1蛋白表达阳性，OS均相同（中位OS 15个月；3年标志性OS 30%；风险比（HR）0.97；95%置信区间，0.44 - 2.10；p值 = 0.93）。在血浆PD-L1阳性队列中，无论组织PD-L1阳性、阴性或未知，OS均无差异（中位OS 15个月；3年标志性OS 30%；HR 1.15；95%置信区间，0.322 - 4.05；p值 = 0.81）。与缺乏PD-L1表达的患者相比，血浆cfRNA表达阳性的患者中位生存期在数值上更长，3年OS更高（中位15个月对8个月；3年标志性OS 30%对15%；HR 0.57，95%置信区间0.26 - 1.20；p值 = 0.11）。
在这项针对真实世界转移性NSCLC患者的回顾性研究中，血浆cfRNA表达与组织PD-L1蛋白表达一样，对ICI获益具有相似的预测价值。
