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Tumor Mutation Burden Correlates With Efficacy of Chemotherapy/Targeted Therapy in Advanced Non-Small Cell Lung Cancer

文献类型：期刊论文

作者Lin, Chen1,2,3; Shi, Xun1,2,3; Zhao, Jun1,2,3; He, Qiong1,2,3; Fan, Yun1,2,3; Xu, Weizhen1,4; Shao, Yang5; Yu, Xinmin1,2,3,6; Jin, Ying1,2,3,7
刊名FRONTIERS IN ONCOLOGY
出版日期2020-04-29
卷号10
关键词tumor mutation burden (TMB) clinical benefit epidermal growth factor receptor tyrosine kinase inhibitors (EGFR-TKIs) chemotherapy non-small cell lung cancer (NSCLC)
ISSN号2234-943X
DOI10.3389/fonc.2020.00480
通讯作者Yu, Xinmin(yuxm@zjcc.org.cn) ; Jin, Ying(jinying@zjcc.org.cn)
英文摘要Objectives:Accumulating evidence has illustrated greater benefit of immunotherapy in tumors with high tumor mutation burden (TMB), whereas its impact on targeted therapy or chemotherapy is undefined. Herein, we evaluated TMB outside of immuno-oncology in epidermal growth factor receptor (EGFR)-mutant patients and EGFR/ALK wild-type cohorts. Methods:In this retrospective study, we correlated TMB with response rate and progression-free survival (PFS) of patients who received EGFR-tyrosine kinase inhibitors (TKIs) or pemetrexed/platinum as first-line therapy. Tumor mutation burden was evaluated by targeted next-generation sequencing. Patients were divided into low (L)/intermediate (I)/high (H) TMB groups by tertiles. Results:In EGFR-mutant cohort, TMB-L patients had a massively improved PFS compared to TMB-I and TMB-H patients (16.4 vs. 9.0 vs. 7.4 months; log-rankp= 0.006) when treated with first-generation EGFR-TKIs. In EGFR/ALK wild-type cohorts who received pemetrexed/platinum regimen, the objective response rate (ORR) of TMB-L group was statistically superior than that of TMB-I and TMB-H groups (53.8% vs. 23% vs. 8.3%; log-rankp= 0.037), and patients with low TMB had a numerically but not significantly prolonged PFS (6.9 vs. 4.3 vs. 4.6 m; log-rankp= 0.22). Conclusion:Our data provide insights into the relevance between TMB and targeted/chemo therapy. Higher non-synonymous TMB correlates with inferior PFS for first-generation EGFR-TKIs in EGFR-driven patients and worse response to pemetrexed/platinum regimen in EGFR/ALK wild-type patients, which has potential clinical implications for cancer treatment but needs corroboration in larger studies.
WOS关键词DNA-DAMAGE ; IMMUNOTHERAPY ; REPAIR ; MULTICENTER ; BIOMARKERS ; RESISTANCE ; IMPACT
资助项目National Natural Science Foundation of China[81702248] ; Zhejiang medical and health science and technology project[2018KY309] ; Natural Science Foundation of Zhejiang Province[LY16H160039]
WOS研究方向Oncology
语种英语
WOS记录号WOS:000557035100001
出版者FRONTIERS MEDIA SA
资助机构National Natural Science Foundation of China ; Zhejiang medical and health science and technology project ; Natural Science Foundation of Zhejiang Province
源URL[http://ir.hfcas.ac.cn:8080/handle/334002/45106]  
专题中国科学院合肥物质科学研究院
通讯作者Yu, Xinmin; Jin, Ying
作者单位1.Chinese Acad Sci, Inst Canc & Basic Med ICBM, Hangzhou, Peoples R China
2.Univ Chinese Acad Sci, Dept Med Oncol, Canc Hosp, Hangzhou, Peoples R China
3.Zhejiang Canc Hosp, Dept Med Oncol, Hangzhou, Peoples R China
4.Zhejiang Canc Hosp, Clin Trials Ctr, Hangzhou, Peoples R China
5.Nanjing Geneseeq Technol Inc, Nanjing, Peoples R China
6.Zhejiang Key Lab Diag & Treatment Technol Thorac, Hangzhou, Peoples R China
7.Zhejiang Key Lab Radiat Oncol, Hangzhou, Peoples R China
推荐引用方式
GB/T 7714		 Lin, Chen,Shi, Xun,Zhao, Jun,et al. Tumor Mutation Burden Correlates With Efficacy of Chemotherapy/Targeted Therapy in Advanced Non-Small Cell Lung Cancer[J]. FRONTIERS IN ONCOLOGY,2020,10.
APA Lin, Chen.,Shi, Xun.,Zhao, Jun.,He, Qiong.,Fan, Yun.,...&Jin, Ying.(2020).Tumor Mutation Burden Correlates With Efficacy of Chemotherapy/Targeted Therapy in Advanced Non-Small Cell Lung Cancer.FRONTIERS IN ONCOLOGY,10.
MLA Lin, Chen,et al."Tumor Mutation Burden Correlates With Efficacy of Chemotherapy/Targeted Therapy in Advanced Non-Small Cell Lung Cancer".FRONTIERS IN ONCOLOGY 10(2020).

入库方式： OAI收割

来源：合肥物质科学研究院

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