Triple-targeted therapy of dabrafenib, trametinib, and osimertinib for the treatment of the acquired BRAF V600E mutation after progression on EGFR-tyrosine kinase inhibitors in advanced EGFR-mutated non-small cell lung cancer patients
机构：[1]Guangdong Cardiovascular Institute, Guangdong Provincial People's Hospital, Guangdong Academy of Medical Sciences, Guangzhou, China.广东省人民医院[2]Guangdong Lung Cancer Institute, Guangdong Provincial People's Hospital (Guangdong Academy of Medical Sciences), Southern Medical University, Guangzhou, China.广东省人民医院[3]Dongguan Institute of Clinical Cancer Research, Dongguan Key Laboratory of Precision Diagnosis and Treatment for Tumors, The Tenth Affiliated Hospital of Southern Medical University (Dongguan People's Hospital), Dongguan, China.[4]National Cancer Center/National Clinical Research Center for Cancer/Cancer Hospital & Shenzhen Hospital, Chinese Academy of Medical Sciences and Perking Union Medical College, Shenzhen, China.深圳市南山区人民医院深圳医学信息中心中国医学科学院肿瘤医院深圳医院[5]Department of Oncology, Shenzhen People's Hospital (The Second Clinical Medical College, Jinan University /The First Affiliated Hospital, Southern University of Science and Technology), Shenzhen, China.深圳市康宁医院深圳市人民医院深圳医学信息中心中国医科大学附属盛京医院中国医科大学盛京医院[6]Department of Pulmonary and Critical Care Medicine, The First Affiliated Hospital of Guangzhou Medical University, Guangzhou Institute of Respiratory Health, State Key Laboratory of Respiratory Disease, National Clinical Research Center for Respiratory Disease /Guangzhou Medical University, Guangzhou, China.[7]Department of Pathology, Guangdong Provincial People's Hospital/Guangdong Academy of Medical Sciences, Southern Medical University, Guangzhou, China.广东省人民医院[8]Guangdong Research Center of Organoid Engineering and Technology, Guangzhou, China.[9]Department of Thoracic Oncology, West China Hospital of Sichuan University, Chengdu, China.四川大学华西医院[10]Division of Pulmonary and Critical Care Medicine, The First Affiliated Hospital of Sun Yat-sen University, Guangzhou, China.中山大学附属第一医院
The B-Raf proto-oncogene, serine/threonine kinase (BRAF) V600E mutation is responsible for approximately 3% of acquired resistance mechanisms to epidermal growth factor receptor (EGFR)-tyrosine kinase inhibitors (TKIs) in advanced EGFR-mutant non-small cell lung cancer (NSCLC). This study investigated the efficacy and safety of a triple-targeted therapy combining EGFR/BRAF/mitogen-activated protein kinase kinase (MEK) inhibitors of dabrafenib, trametinib, and osimertinib in NSCLC patients with acquired BRAF V600E mutation after EGFR-TKI treatment.A multi-center retrospective review of medical records was performed to analyze EGFR-mutated advanced Chinese NSCLC patients who acquired the BRAF V600E mutation following EGFR-TKI treatment. All patients subsequently received dabrafenib, trametinib, and osimertinib. The clinical characteristics, progression-free survival (PFS), and adverse events (AEs) were documented. The in-vivo drug response of patient-derived organoids (PDOs) was observed. Next-generation sequencing (NGS) was performed upon progression to triple-targeted therapy.Thirteen patients with BRAF V600E mutations were included. Following triple-targeted therapy, the corresponding objective response rate and disease control rate were 61.5% and 92.3%, respectively. The median PFS was 13.5 months (95% confidence interval: 6.6-20.4). PDOs derived from one patient's tumor sample were established, revealing that the triple-targeted therapy had a significantly lower half-maximal inhibitory concentration (IC50) value compared to other regimens. The tumor growth inhibitory rate was 99.36% for dabrafenib, trametinib, and osimertinib; 99.25% for osimertinib plus vemurafenib; 98.92% for osimertinib, encorafenib, and cetuximab; and 62.83% for pemetrexed plus carboplatin. NGS analysis identified major resistance mechanisms following the triple-targeted therapy, including the EGFR-dependent pathway, EGFR and BRAF V600E-dependent pathway, and an off-target mechanism.EGFR/BRAF/MEK triple-targeted therapy is an effective and safe approach for treating EGFR-mutated NSCLC patients resistant to EGFR-TKIs with acquired BRAF V600E mutations.2024 AME Publishing Company. All rights reserved.
基金：
National Natural Science Foundation of China (No. 81972164 to J.J.Y.) and Guangdong Provincial Key Laboratory of Lung Cancer
Translational Medicine (No. 2017B030314120).
语种：
外文
PubmedID：
中科院(CAS)分区：
出版当年[2024]版：
无
最新[2023]版：
大类|2 区医学
小类|3 区肿瘤学3 区呼吸系统
第一作者：
第一作者机构：[1]Guangdong Cardiovascular Institute, Guangdong Provincial People's Hospital, Guangdong Academy of Medical Sciences, Guangzhou, China.[2]Guangdong Lung Cancer Institute, Guangdong Provincial People's Hospital (Guangdong Academy of Medical Sciences), Southern Medical University, Guangzhou, China.
共同第一作者：
通讯作者：
通讯机构：[1]Guangdong Cardiovascular Institute, Guangdong Provincial People's Hospital, Guangdong Academy of Medical Sciences, Guangzhou, China.[2]Guangdong Lung Cancer Institute, Guangdong Provincial People's Hospital (Guangdong Academy of Medical Sciences), Southern Medical University, Guangzhou, China.
推荐引用方式(GB/T 7714)：
Weng Cheng-Di,Liu Ke-Jun,Jin Shi,et al.Triple-targeted therapy of dabrafenib, trametinib, and osimertinib for the treatment of the acquired BRAF V600E mutation after progression on EGFR-tyrosine kinase inhibitors in advanced EGFR-mutated non-small cell lung cancer patients[J].Translational Lung Cancer Research.2024,13(10):2538-2548.doi:10.21037/tlcr-24-358.
APA：
Weng Cheng-Di,Liu Ke-Jun,Jin Shi,Su Jun-Wei,Yao Yi-Hui...&Yang Jin-Ji.(2024).Triple-targeted therapy of dabrafenib, trametinib, and osimertinib for the treatment of the acquired BRAF V600E mutation after progression on EGFR-tyrosine kinase inhibitors in advanced EGFR-mutated non-small cell lung cancer patients.Translational Lung Cancer Research,13,(10)
MLA：
Weng Cheng-Di,et al."Triple-targeted therapy of dabrafenib, trametinib, and osimertinib for the treatment of the acquired BRAF V600E mutation after progression on EGFR-tyrosine kinase inhibitors in advanced EGFR-mutated non-small cell lung cancer patients".Translational Lung Cancer Research 13..10(2024):2538-2548
