Concomitant Mutations in EGFR 19Del/L858R Mutation and Their Association with Response to EGFR-TKIs in NSCLC Patients

Overview

Journal Cancer Manag Res

Publisher Dove Medical Press

Specialty Oncology

Date 2020 Sep 28

PMID 32982456

Citations 10

Authors

Hengrui Liang

Caichen Li

Yi Zhao

Shen Zhao

Jun Huang

Xiuyu Cai

Bo Cheng

Shan Xiong

Jianfu Li

Wei Wang

Changbin Zhu

Weiwei Li

Jianxing He

Wenhua Liang

Affiliations

Soon will be listed here.

Abstract

Objective: Differences in efficacy of epidermal growth factor receptor-tyrosine kinase inhibitors (EGFR-TKI) have been observed between non-small cell lung cancer (NSCLC) patients with and mutation. We explored whether the total number or pattern of concomitant mutations of and may explain their different sensitivities.

Patients And Methods: This study contained the mutational profiles of EGFR-mutated NSCLC patients from two cohorts: Guangzhou (G1) and database (G2). Concomitant mutation status and EGFR-TKI response information were retrieved.

Results: A total of 403 patients covered 283 genes in the G1 and 803 patients with a different gene set in the G2 were included. Similar prevalence of total concomitant mutation number was observed in both G1 ( 32.48% vs 30.45%; =0.68) and G2 ( 74.9% vs 73.2%; =0.65) cohorts. Only pathway same more related to mutation. EGFR-TKI response information was recorded for 134 patients in the G2 cohort. showed a higher objective response (OR) rate compared with , regardless of concomitant mutations. Compared to patients with OR, non-OR patients had more concomitant mutations, both in (53.8% vs 83.3%; =0.021) and (51.4% vs 77.8%; =0.029). In particular, total concomitant mutations (OR=0.27; =0.03), sensitive mutations (OR=2.21; =0.04), and (OR=0.244; =0.02) significantly affected the TKI response.

Conclusion: Concomitant mutations were widespread in and and were associated with poorer OR to EGFR-TKIs. However, and had similar numbers and patterns of concomitant mutations, which might not explain the different sensitivity to EGFR-TKI.

Citing Articles

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References

Cheng Y, Stefaniuk C, Jakubowski M . Real-time PCR and targeted next-generation sequencing in the detection of low level mutations: Instructive case analyses. Respir Med Case Rep. 2019; 28:100901. PMC: 6656700. DOI: 10.1016/j.rmcr.2019.100901. View

Yu J, Yu S, Wang S, Bai H, Zhao J, An T . Clinical outcomes of EGFR-TKI treatment and genetic heterogeneity in lung adenocarcinoma patients with EGFR mutations on exons 19 and 21. Chin J Cancer. 2016; 35:30. PMC: 4802875. DOI: 10.1186/s40880-016-0086-2. View

Tan C, Gilligan D, Pacey S . Treatment approaches for EGFR-inhibitor-resistant patients with non-small-cell lung cancer. Lancet Oncol. 2015; 16(9):e447-e459. DOI: 10.1016/S1470-2045(15)00246-6. View

Liao L, Ji X, Ge M, Zhan Q, Huang R, Liang X . Characterization of genetic alterations in brain metastases from non-small cell lung cancer. FEBS Open Bio. 2018; 8(9):1544-1552. PMC: 6120240. DOI: 10.1002/2211-5463.12501. View

Hong S, Gao F, Fu S, Wang Y, Fang W, Huang Y . Concomitant Genetic Alterations With Response to Treatment and Epidermal Growth Factor Receptor Tyrosine Kinase Inhibitors in Patients With EGFR-Mutant Advanced Non-Small Cell Lung Cancer. JAMA Oncol. 2018; 4(5):739-742. PMC: 5885210. DOI: 10.1001/jamaoncol.2018.0049. View

Hou H, Yang X, Zhang J, Zhang Z, Xu X, Zhang X . Discovery of targetable genetic alterations in advanced non-small cell lung cancer using a next-generation sequencing-based circulating tumor DNA assay. Sci Rep. 2017; 7(1):14605. PMC: 5668369. DOI: 10.1038/s41598-017-14962-0. View

Tian P, Wang Y, Wang W, Li Y, Wang K, Cheng X . High-throughput sequencing reveals distinct genetic features and clinical implications of NSCLC with de novo and acquired EGFR T790M mutation. Lung Cancer. 2018; 124:205-210. DOI: 10.1016/j.lungcan.2018.08.014. View

Yu H, Suzawa K, Jordan E, Zehir A, Ni A, Kim R . Concurrent Alterations in EGFR-Mutant Lung Cancers Associated with Resistance to EGFR Kinase Inhibitors and Characterization of MTOR as a Mediator of Resistance. Clin Cancer Res. 2018; 24(13):3108-3118. PMC: 6420806. DOI: 10.1158/1078-0432.CCR-17-2961. View

Jin Y, Shi X, Zhao J, He Q, Chen M, Yan J . Mechanisms of primary resistance to EGFR targeted therapy in advanced lung adenocarcinomas. Lung Cancer. 2018; 124:110-116. DOI: 10.1016/j.lungcan.2018.07.039. View

10.

Sato S, Nagahashi M, Koike T, Ichikawa H, Shimada Y, Watanabe S . Impact of Concurrent Genomic Alterations Detected by Comprehensive Genomic Sequencing on Clinical Outcomes in East-Asian Patients with EGFR-Mutated Lung Adenocarcinoma. Sci Rep. 2018; 8(1):1005. PMC: 5772517. DOI: 10.1038/s41598-017-18560-y. View

11.

Martorell P, Huerta M, Compan Quilis A, Abellan R, Seda E, Blesa S . Coexistence of EGFR, KRAS, BRAF, and PIK3CA Mutations and ALK Rearrangement in a Comprehensive Cohort of 326 Consecutive Spanish Nonsquamous NSCLC Patients. Clin Lung Cancer. 2017; 18(6):e395-e402. DOI: 10.1016/j.cllc.2017.04.006. View

12.

Reynolds J, Zhou Y, Jakubowski M, Wang Z, Brainard J, Klein R . Next-generation sequencing of liquid-based cytology non-small cell lung cancer samples. Cancer Cytopathol. 2017; 125(3):178-187. DOI: 10.1002/cncy.21812. View

13.

Blakely C, Watkins T, Wu W, Gini B, Chabon J, McCoach C . Evolution and clinical impact of co-occurring genetic alterations in advanced-stage EGFR-mutant lung cancers. Nat Genet. 2017; 49(12):1693-1704. PMC: 5709185. DOI: 10.1038/ng.3990. View

14.

Yang J, Wu Y, Schuler M, Sebastian M, Popat S, Yamamoto N . Afatinib versus cisplatin-based chemotherapy for EGFR mutation-positive lung adenocarcinoma (LUX-Lung 3 and LUX-Lung 6): analysis of overall survival data from two randomised, phase 3 trials. Lancet Oncol. 2015; 16(2):141-51. DOI: 10.1016/S1470-2045(14)71173-8. View

15.

VanderLaan P, Rangachari D, Mockus S, Spotlow V, Reddi H, Malcolm J . Mutations in TP53, PIK3CA, PTEN and other genes in EGFR mutated lung cancers: Correlation with clinical outcomes. Lung Cancer. 2017; 106:17-21. PMC: 5351777. DOI: 10.1016/j.lungcan.2017.01.011. View

16.

Xu Y, Tong X, Yan J, Wu X, Shao Y, Fan Y . Short-Term Responders of Non-Small Cell Lung Cancer Patients to EGFR Tyrosine Kinase Inhibitors Display High Prevalence of TP53 Mutations and Primary Resistance Mechanisms. Transl Oncol. 2018; 11(6):1364-1369. PMC: 6132175. DOI: 10.1016/j.tranon.2018.08.010. View

17.

Singh M, Jadhav H . Targeting non-small cell lung cancer with small-molecule EGFR tyrosine kinase inhibitors. Drug Discov Today. 2017; 23(3):745-753. DOI: 10.1016/j.drudis.2017.10.004. View

18.

da Cunha Santos G, Shepherd F, Tsao M . EGFR mutations and lung cancer. Annu Rev Pathol. 2010; 6:49-69. DOI: 10.1146/annurev-pathol-011110-130206. View

19.

Liu L, Liu J, Shao D, Deng Q, Tang H, Liu Z . Comprehensive genomic profiling of lung cancer using a validated panel to explore therapeutic targets in East Asian patients. Cancer Sci. 2017; 108(12):2487-2494. PMC: 5715245. DOI: 10.1111/cas.13410. View

20.

Li W, Qiu T, Guo L, Ling Y, Gao Y, Ying J . Primary and acquired EGFR T790M-mutant NSCLC patients identified by routine mutation testing show different characteristics but may both respond to osimertinib treatment. Cancer Lett. 2018; 423:9-15. DOI: 10.1016/j.canlet.2018.03.005. View