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Rare EGFR E709-T710delinsX: Molecular characteristics and superior response to afatinib treatment in NSCLC patients

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机构: [a]Department of Medical Oncology, State Key Laboratory of Oncology in South China, Collaborative Innovation Center for Cancer Medicine, Sun Yat-Sen University Cancer Center, Guangzhou 510060, People’s Republic of China [b]Department of Respiratory Medicine, Jinling Hospital, Nanjing University School of Medicine, 305 Zhongshan Road, Nanjing 210002, People’s Republic of China [c]Department of Respiratory and Critical Care, Guangdong Provincial People’s Hospital, Guangdong Academy of Medical Sciences, Guangzhou 510060, People’s Republic of China [d]Department of Chemotherapy, Chinese Academy of Sciences University Cancer Hospital, No. 1 Banshan East Street, Gongshu District, Hangzhou 310022, People’s Republic of China [e]Department of Oncology, The First Affiliated Hospital of Zhengzhou University, Zhengzhou 450052, People’s Republic of China [f]Department of Medical Oncology, Lung Cancer and Gastrointestinal Unit, Hunan Cancer Hospital, The Affiliated Cancer Hospital of Xiangya School of Medicine, Central South University, Changsha 410013, People’s Republic of China [g]Department of Medical Oncology, Sichuan Cancer Hospital & Institute, Sichuan Cancer Center, School of Medicine, University of Electronic Science and Technology of China, 4th Section, People’s South Road, Chengdu 610041, People’s Republic of China [h]Department of Respiratory Medicine, Zhongda Hospital Southeast University, Nanjing 210009, People’s Republic of China [i]The First Affiliated Hospital of Jiaxing University, Jiaxing 314000, People’s Republic of China [j]The First Affiliated Hospital of Guangzhou Medical University, Guangzhou 510120, People’s Republic of China k Radiotherapy Center, Jiangmen Central Hospital, Jiangmen 529020, People’s Republic of China
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关键词: Non-small-cell lung cancer EGFR E709-T710delinsX Tyrosine kinase inhibitors Chemotherapy

摘要:
Currently, whether patients with rare epidermal growth factor receptor (EGFR) mutations could benefit from EGFR tyrosine kinase inhibitors (TKIs) demands further studies. Limited clinical data are available regarding the molecular characteristics and clinical response in non-small-cell lung cancer (NSCLC) patients harboring EGFR E709-T710delinsX mutations, a rare mutation type in exon 18 of EGFR. In this study, we aimed to explore the molecular distribution and clinical outcome of EGFR E709-T710delinsX mutated Chinese patients.Next-generation sequencing (NGS) tests were performed in 15,078 NSCLC patients. A multicenter retrospective cohort involving 17 advanced lung cancer patients with EGFR E709-T710delinsX was collected to evaluate clinical responses to diverse therapies. In silico protein structure modeling was conducted to predict drug response.5905 EGFR mutant patients (39.2%, 5905/15078) were identified, with 26 cases (0.44%, 26/5905) harbored EGFR E709-T710delinsD. Afatinib showed a better overall objective response rate (ORR) compared with the first-generation (1G) EGFR TKIs and chemotherapy with significant difference. Superior progression free survival (PFS) was also observed in patients treated with afatinib (afatinib 10.85 m vs 1G EGFR TKIs 4.0 m vs chemotherapy 2.8 m, p = 0.0007). In silico protein structure modeling predicts better binding of afatinib with EGFR E709-T710delinsD compared with other EGFR TKIs.This is the largest studies for EGFR E709-T710delinsX, with 26 cases with EGFR E709-T710delinsX being identified (0.44% in EGFR mutant NSCLC, 0.17% in NSCLC patients). This study also firstly revealed that afatinib might exert superior antitumor activity to the 1G EGFR TKIs and chemotherapy in EGFR E709-T710delinsX mutant patients.Copyright © 2022 Elsevier B.V. All rights reserved.

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大类 | 2 区 医学
小类 | 2 区 呼吸系统 2 区 肿瘤学
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大类 | 2 区 医学
小类 | 3 区 肿瘤学 3 区 呼吸系统
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Q2 ONCOLOGY Q2 RESPIRATORY SYSTEM
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第一作者机构: [a]Department of Medical Oncology, State Key Laboratory of Oncology in South China, Collaborative Innovation Center for Cancer Medicine, Sun Yat-Sen University Cancer Center, Guangzhou 510060, People’s Republic of China
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