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PDL1 高表达且无 TP53、KEAP1 和 EPHA5 突变的非小细胞肺癌患者接受阿替利珠单抗治疗后生存获益更好。

PDL1 high expression without TP53, KEAP1 and EPHA5 mutations could better predict survival for patients with NSCLC receiving atezolizumab.

机构信息

Department of Internal Medicine-Oncology, Shandong Cancer Hospital and Institute, Shandong First Medical University and Shandong Academy of Medical Sciences, Jinan 250117, China.

Department of Pathology, Shandong Cancer Hospital and Institute, Shandong First Medical University and Shandong Academy of Medical Sciences, Jinan 250117, China.

出版信息

Lung Cancer. 2021 Jan;151:76-83. doi: 10.1016/j.lungcan.2020.11.006. Epub 2020 Nov 13.

Abstract

BACKGROUND

Non-small cell lung cancer (NSCLC) patients with high expression of PDL1 are more likely to benefit from atezolizumab. There are no relevant research focusing on the relationship between the PDL1 expression and clinical variables and gene mutation types among NSCLC patients.

METHODS

NSCLC patients with confirmed PDL1 expression and gene mutation information from OAK study were included in our study. Logistic regression proportional model was applied to analyze the risk factors on PDL1 high expression. The biomarker evaluable population (BEP) was screened to analyze the gene mutation informaion among these patients. High frequency gene mutations were screened based on different PDL1 expressions. Moreover, the log rank test was applied to analyze the overall survival (OS) difference based on different gene mutation types.

RESULTS

A total of 838 patients with NSCLC were included in our study. White patients are more likely to have PDL1 ≥ 1% (P = 0.004). ERBB4, EP300, PREX2, SLIT2, EPHB1 and IGF2R mutations were high frequency mutations in patients with high PDL1 expression, and the patients with EGFR, SMARCA4, EPHA5, FAT1, STK11, TET2 mutations were more likely to be seen in negative PDL1 expression group. Worse survival could be found in patients with KEAP1 (P < 0.001), TP53 (P = 0.004) and EPHA5 (P = 0.013) mutations who received atezolizumab compared with those who had none of these gene mutations. Importantly, for PDL1 high patients without KEAP1, EPHA5, TP53 mutations receiving atezolizumab, they all showed relatively longer median survival with 22.47, 22.18 and 23.33 months, respectively (all, P < 0.01).

CONCLUSIONS

Different high frequency gene mutations could be found between the patients with high and negative PDL1. PDL1 expression combined with specific gene mutation may better predict the survival for patients receiving atezolizumab.

摘要

背景

高表达 PD-L1 的非小细胞肺癌(NSCLC)患者可能从阿特珠单抗治疗中获益更多。目前尚无相关研究聚焦 NSCLC 患者的 PD-L1 表达与临床变量和基因变异类型之间的关系。

方法

纳入 OAK 研究中 PD-L1 表达和基因变异信息明确的 NSCLC 患者,应用 logistic 回归比例模型分析 PD-L1 高表达的影响因素。筛选出生物标志物可评估人群(BEP),分析这些患者的基因变异信息。根据不同 PD-L1 表达筛选高频基因变异,并采用对数秩检验分析不同基因变异类型患者的总生存(OS)差异。

结果

共纳入 838 例 NSCLC 患者,白种人更可能有 PD-L1≥1%(P=0.004)。PD-L1 高表达患者中高频突变基因包括 ERBB4、EP300、PREX2、SLIT2、EPHB1 和 IGF2R,而 EGFR、SMARCA4、EPHA5、FAT1、STK11、TET2 基因突变更常见于 PD-L1 低表达组。与未发生这些基因变异的患者相比,接受阿特珠单抗治疗的 KEAP1(P<0.001)、TP53(P=0.004)和 EPHA5(P=0.013)突变患者的生存更差。重要的是,对于未发生 KEAP1、EPHA5、TP53 突变的 PD-L1 高表达患者,接受阿特珠单抗治疗后中位生存时间分别为 22.47、22.18 和 23.33 个月(均 P<0.01)。

结论

PD-L1 高表达和低表达患者之间可能存在不同的高频基因变异。PD-L1 表达结合特定基因变异可能更好地预测接受阿特珠单抗治疗患者的生存情况。

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