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Immune microenvironment features and efficacy of PD-1/PD-L1 blockade in non-small cell lung cancer patients with EGFR or HER2 exon 20 insertions

文献类型：期刊论文

作者Chen, Kaiyan2,3,4; Pan, Guoqiang2,3,4; Cheng, Guoping2,3,5; Zhang, Fanrong2,3,6; Xu, Yanjun2,3,4; Huang, Zhiyu2,3,4; Fan, Yun1,2,3,4
刊名THORACIC CANCER
出版日期2020-11-18
ISSN号1759-7706
关键词EGFR HER2 immunotherapy NSCLC PD‐ L1
DOI10.1111/1759-7714.13748
通讯作者Fan, Yun(fanyun@zjcc.org.cn)
英文摘要Background Insertions in exon 20 (Ex20ins) of epidermal growth factor receptor (EGFR) and human epidermal growth factor receptor 2 (HER2) are relatively insensitive to first- and second-generation EGFR-tyrosine kinase inhibitors (TKIs) in non-small cell lung cancer (NSCLC). This study aimed to investigate the immune microenvironment features and efficacy of PD-1/PD-L1 blockade of NSCLC with EGFR and HER2 Ex20ins. Methods Clinical characteristics, coexisting mutations, and outcomes to EGFR-TKIs and immune checkpoint blockade were reviewed for NSCLC patients with exon 20 mutations of EGFR or HER2. Data obtained included the molecular spectrum (extended genotyping for mutations in 324 cancer-related genes), as well as tumor mutational burden (TMB), PD-L1 protein expression, and the abundance of CD4+ and CD8+ tumor-infiltrating lymphocytes (TILs). Results A total of 1270 NSCLC patients were identified. Of these, 504 (39.7%) cases had EGFR mutations and 6.9% (35/504) of them had EGFR Ex20ins. Meanwhile, 21 (1.7%) cases with HER2 Ex20ins were detected. Comprehensive genomic profiling identified A767_V769dup variant (25.0%) was the most common type in tumors with EGFR Ex20ins. Co-occurring mutations were not uncommon including TP53 (45%), PIK3CA (20%), CDKN2A (10%), and EGFR amplification (20%). The average TMB was 3.3 mutations/megabase. PD-L1 expression in patients with EGFR Ex20ins was significantly higher than for those with HER2 mutations (48.6% vs. 19.0%, P = 0.027). High TMB and PD-L1 expression was independently associated with significantly poor prognosis (P = 0.025, P = 0.045, respectively) while there was no association between CD4+/CD8+ TILs and prognosis in EGFR or HER2 mutant NSCLC. Finally, patients harboring EGFR Ex20ins seemed to be sensitive to PD-1/PD-L1 blockage whereas it showed limited efficacy in patients with HER2 Ex20ins. Conclusions NSCLC patients with EGFR/HER2 Ex20ins had similar genomic characteristics and distinct immune features. Patients with EGFR Ex20ins had significantly higher PD-L1 expression than those with HER2 mutations, which may be the potential reason for the different responses to PD-1/PD-L1 blockage.
WOS关键词OPEN-LABEL ; MUTATIONS ; ADENOCARCINOMAS ; OUTCOMES ; PHASE-3 ; CHEMOTHERAPY ; INHIBITORS
资助项目Basic Public Foundation of Zhejiang Province of China[LGF18H160017]
WOS研究方向Oncology ; Respiratory System
语种英语
出版者WILEY
WOS记录号WOS:000590174500001
资助机构Basic Public Foundation of Zhejiang Province of China
源URL[http://ir.hfcas.ac.cn:8080/handle/334002/105326]  
专题中国科学院合肥物质科学研究院
通讯作者Fan, Yun
作者单位1.Wenzhou Med Univ, Dept Oncol, First Clin Med Coll, Wenzhou 325000, Peoples R China
2.Univ Chinese Acad Sci, Canc Hosp, Zhejiang Canc Hosp, Hangzhou, Peoples R China
3.Chinese Acad Sci, Inst Basic Med & Canc IBMC, Hangzhou, Peoples R China
4.Zhejiang Canc Hosp, Dept Thorac Med Oncol, Hangzhou, Peoples R China
5.Zhejiang Canc Hosp, Dept Pathol, Hangzhou, Peoples R China
6.Zhejiang Canc Hosp, Dept Breast Surg, Hangzhou, Peoples R China
推荐引用方式
GB/T 7714		 Chen, Kaiyan,Pan, Guoqiang,Cheng, Guoping,et al. Immune microenvironment features and efficacy of PD-1/PD-L1 blockade in non-small cell lung cancer patients with EGFR or HER2 exon 20 insertions[J]. THORACIC CANCER,2020.
APA Chen, Kaiyan.,Pan, Guoqiang.,Cheng, Guoping.,Zhang, Fanrong.,Xu, Yanjun.,...&Fan, Yun.(2020).Immune microenvironment features and efficacy of PD-1/PD-L1 blockade in non-small cell lung cancer patients with EGFR or HER2 exon 20 insertions.THORACIC CANCER.
MLA Chen, Kaiyan,et al."Immune microenvironment features and efficacy of PD-1/PD-L1 blockade in non-small cell lung cancer patients with EGFR or HER2 exon 20 insertions".THORACIC CANCER (2020).

入库方式： OAI收割

来源：合肥物质科学研究院

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