东亚非小细胞肺癌患者中常规 22C3 检测 PD-L1 表达的分布和一致性。

Distribution and concordance of PD-L1 expression by routine 22C3 assays in East-Asian patients with non-small cell lung cancer.

机构信息

Department of Thoracic Surgery and State Key Laboratory of Genetic Engineering, Fudan University Shanghai Cancer Center, 270 Dong-An Road, Shanghai, 200032, China.

Institute of Thoracic Oncology, Fudan University, Shanghai, 200032, China.

出版信息

Respir Res. 2022 Nov 5;23(1):302. doi: 10.1186/s12931-022-02201-8.

BACKGROUND

Currently, programmed death ligand-1 (PD-L1) expression has been widely applied in clinical trials and real-world clinical practice as a major biomarker for the efficacy of immune-checkpoint inhibitors. The purpose of this study is to reveal the distribution and concordance of PD-L1 expression in a large-scale consecutive cohort from East-Asian patients with non-small cell lung cancer (NSCLC).

METHODS

PD-L1 testing was conducted using 22C3 assays, and cases were categorized into the high, low, and no expression of PD-L1 based on the tumor proportion score (TPS). Target-capture next-generation sequencing was used to identify molecular events.

RESULTS

A total of 4550 patients and 4622 tests of PD-L1 expression were enrolled. There were 3017 (66.3%) patients with no PD-L1 expression (TPS < 1%), 1013 (22.3%) with low PD-L1 expression (TPS 1-49%), 520 (11.4%) with high PD-L1 expression (TPS ≥ 50%). Higher proportions of positive PD-L1 expression (TPS ≥ 1%) were observed in smokers, males, squamous cell carcinoma, and high-grade lung adenocarcinoma. Further analyses revealed fair agreement in primary and metastatic lesions (kappa = 0.533), poor agreement in multi-focal primary tumors (kappa = 0.045), and good agreement in biopsy and resection samples (kappa = 0.662) / two biopsy samples (kappa = 0.711). Mutational analyses revealed association between high PD-L1 expression (TPS ≥ 50%) and EGFR wild-type, KRAS mutation, ALK rearrangement, and TP53 mutation.

CONCLUSION

The study reveals the unique distribution pattern of PD-L1 expression in a large-scale East-Asian cohort with NSCLC, the concordance of multiple PD-L1 tests, and the association between PD-L1 expression and molecular events. The results shed a light on the optimization of PD-L1 testing in clinical practice.

背景

目前，程序性死亡配体-1（PD-L1）表达已广泛应用于临床试验和真实世界的临床实践中，作为免疫检查点抑制剂疗效的主要生物标志物。本研究旨在揭示大规模连续东亚非小细胞肺癌（NSCLC）患者群体中 PD-L1 表达的分布和一致性。

方法

使用 22C3 检测法进行 PD-L1 检测，并根据肿瘤比例评分（TPS）将病例分为 PD-L1 高、低和无表达。采用靶向捕获下一代测序来鉴定分子事件。

结果

共纳入 4550 例患者和 4622 例 PD-L1 表达检测。3017 例（66.3%）患者无 PD-L1 表达（TPS<1%），1013 例（22.3%）患者低 PD-L1 表达（TPS 1-49%），520 例（11.4%）患者高 PD-L1 表达（TPS≥50%）。在吸烟者、男性、鳞状细胞癌和高级别肺腺癌中观察到更高比例的阳性 PD-L1 表达（TPS≥1%）。进一步分析显示，原发和转移病变之间具有良好的一致性（kappa=0.533），多灶性原发肿瘤之间一致性较差（kappa=0.045），活检和切除样本之间具有良好的一致性（kappa=0.662）/两个活检样本之间具有高度一致性（kappa=0.711）。突变分析显示，高 PD-L1 表达（TPS≥50%）与 EGFR 野生型、KRAS 突变、ALK 重排和 TP53 突变有关。