PD-L1 Expression and Outcome in Patients with Metastatic Non-Small Cell Lung Cancer and EGFR Mutations Receiving EGFR-TKI as Frontline Treatment.
PD-L1 Expression and Outcome in Patients with Metastatic Non-Small Cell Lung Cancer and EGFR Mutations Receiving EGFR-TKI as Frontline Treatment.
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DOI：
10.2147/ott.s290445
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发表时间：
2021
影响因子：
4
通讯作者：
Chang SC
中科院分区：
文献类型：
--
作者：
Chang CY;Lai YC;Wei YF;Chen CY;Chang SC
表皮生长因子受体（EGFR）突变在东亚最常见，据报道频率为30-50%。EGFR-酪氨酸激酶抑制剂（TKI）被推荐作为具有致敏EGFR突变的非小细胞肺癌（NSCLC）的一线治疗选择。几种免疫检查点抑制剂已成功改善晚期肺癌的预后。肿瘤细胞上程序性细胞死亡配体1（PD-L1）的表达在预测程序性细胞死亡蛋白1/PD-L1抑制剂的疗效中起重要作用。PD-L1表达在EGFR突变肿瘤中的作用及其对临床结局的影响仍存在争议。本回顾性研究入组了接受标准治疗（即EGFR-TKI作为突变型腺癌的一线治疗）的新诊断转移性NSCLC伴致敏EGFR突变患者。分别采用Cobas RT-PCR和Dako 22 C3免疫组化染色检测EGFR突变和PD-L1表达水平。2011年1月至2019年2月，入组了114例患者。平均年龄为62岁（范围34-92岁），45例（39.5%）患者为男性。在这些患者中，EGFR突变分析显示55例（48.2%）患者存在外显子19框内缺失，53例（46.5%）患者存在外显子21 L 858 R，6例（5.3%）患者存在不常见突变。在这些EGFR突变患者中，54例（46.9%）患者的肿瘤比例评分（TPS）PD-L1表达水平<1%，50例（44.2%）患者为1-49%，10例（8.8%）患者≥50%。所有患者均接受EGFR-TKI作为一线治疗，在Kaplan-Meier分析中，不同PD-L1表达状态的组间无进展生存期无显著差异。对于转移性NSCLC和EGFR突变患者，PD-L1表达并不罕见，但在接受标准初始治疗的患者中未观察到对临床结局的显著影响。
Epidermal growth factor receptor (EGFR) mutations are most common in Eastern Asia, and frequencies of 30–50% have been reported. EGFR-tyrosine kinase inhibitors (TKIs) are recommended as first-line therapeutic options for non-small cell lung cancer (NSCLC) with sensitizing EGFR mutations. Several immune checkpoint inhibitors have been successful in improving the outcomes of advanced lung cancer. The expression of programmed cell death-ligand 1 (PD-L1) on tumor cells plays an important role in predicting the efficacy of programmed cell death protein 1/PD-L1 inhibitors. The role of PD-L1 expression in tumors with EGFR mutation and its influence on clinical outcomes remain controversial. Patients with newly diagnosed metastatic NSCLC with sensitizing EGFR mutations who received the standard treatment, ie, EGFR-TKIs for mutant adenocarcinoma as the first-line treatment, were enrolled in this retrospective study. EGFR mutations and PD-L1 expression levels were detected by Cobas RT-PCR and Dako 22C3 immunohistochemistry staining, respectively. From January 2011 to February 2019, 114 patients were enrolled. The average age was 62 years (range 34–92), and 45 (39.5%) patients were male. Among these patients, EGFR mutation analysis revealed exon 19 in-frame deletion in 55 (48.2%) patients, exon 21 L858R in 53 (46.5%) patients, and uncommon mutations in 6 (5.3%) patients. Among these patients with EGFR mutations, PD-L1 expression levels by tumor proportion score (TPS) were <1% in 54 (46.9%) patients, 1–49% in 50 (44.2%) patients, and ≥50% in 10 (8.8%) patients. All patients received EGFR-TKIs as first-line treatment, and in the Kaplan-Meier analysis, progression-free survival was not significantly different among groups with different PD-L1 expression status. For patients with metastatic NSCLC and EGFR mutations, PD-L1 expression is not uncommon, but no significant influence on clinical outcomes was observed in patients receiving standard initial treatment.