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

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

doi:10.2147/CMAR.S255967

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

Cancer Manag Res. 2020 Sep 18:12:8653-8662. doi: 10.2147/CMAR.S255967. eCollection 2020.

Authors

Hengrui Liang^#¹, Caichen Li^#¹, Yi Zhao^#¹, Shen Zhao^#², Jun Huang¹, Xiuyu Cai^{2

3}, Bo Cheng¹, Shan Xiong¹, Jianfu Li¹, Wei Wang¹, Changbin Zhu⁴, Weiwei Li⁵, Jianxing He¹, Wenhua Liang¹

Affiliations

¹ Department of Thoracic Surgery and Oncology, The First Affiliated Hospital of Guangzhou Medical University, State Key Laboratory of Respiratory Disease, National Clinical Research Center for Respiratory Disease, Guangzhou Institute of Respiratory Health, Guangzhou, People's Republic of China.
² Department of Medical Oncology, Sun Yat-Sen University Cancer Center, State Key Laboratory of Oncology in South China, Collaborative Innovation Center for Cancer Medicine, Guangzhou, People's Republic of China.
³ Department of General Internal Medicine, Sun Yat-Sen University Cancer Center, State Key Laboratory of Oncology in South China, Collaborative Innovation Center for Cancer Medicine, Guangzhou, People's Republic of China.
⁴ BGI Genomics, BGI-Shenzhen, Shenzhen 518083, People's Republic of China.
⁵ BGI-Guangzhou Medical Laboratory, BGI-Shenzhen, Guangzhou 510006, People's Republic of China.

^# Contributed equally.

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 19 exon deletion (19Del) and L858R mutation. We explored whether the total number or pattern of concomitant mutations of 19Del and L858R 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 (19Del 32.48% vs L858R 30.45%; P=0.68) and G2 (19Del 74.9% vs L858R 73.2%; P=0.65) cohorts. Only HGF/c-Met pathway same more related to L858R mutation. EGFR-TKI response information was recorded for 134 patients in the G2 cohort. 19Del showed a higher objective response (OR) rate compared with L858R, regardless of concomitant mutations. Compared to patients with OR, non-OR patients had more concomitant mutations, both in 19Del (53.8% vs 83.3%; P=0.021) and L858R (51.4% vs 77.8%; P=0.029). In particular, total concomitant mutations (OR=0.27; P=0.03), sensitive EGFR mutations (OR=2.21; P=0.04), and T790M (OR=0.244; P=0.02) significantly affected the TKI response.

Conclusion: Concomitant mutations were widespread in 19Del and L858R and were associated with poorer OR to EGFR-TKIs. However, 19Del and L858R had similar numbers and patterns of concomitant mutations, which might not explain the different sensitivity to EGFR-TKI.

Keywords: 19Del; L858R; concomitant mutation; epidermal growth factor receptor mutation; non-small cell lung cancer.

Grants and funding

This work was supported by the following funding: the grant 2016YFC0905400 from the National Key R&D Program of China; China National Science Foundation (Grant No. 81871893 & No. 81501996); Key Project of Guangzhou Scientific Research Project (Grant No. 201804020030); High-level university construction project of Guangzhou Medical University (Grant No. 20182737, 201721007, 201715907, 2017160107); National key R & D Program (Grant No. 2017YFC0907903 & 2017YFC0112704).