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RET-AREAL: A multi-center, real-world data analysis on the efficacy of pralsetinib in acquired RET fusion after resistance to EGFR/ALK-TKIs

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收录情况： ◇ SCIE

作者：
Tang Xinjun[1] * ; Hu Jie[1,2] * ; Guo Renhua[3] ; Wang Yina[4] ; Yao Yu[5] ; Zeng Liang[6] ; Wang Haitao[7] ; Shen Haibo[8] ; Chen Jun[9] ; Huang Weina[10] ; Liu Lihua[11] ; Su Ming[12] ; Yu Zhuang[13] ; Mao Weidong[14] ; Wang Jinliang[15] ; Tao Haitao[15] ; Dong Guilan[16] ; Cai Chang[17] ; Xie Yupeng[17] ; Qu Tao[18] ; Zhang Yan[19] ; Shen Wei[20] ; Cao Jing[21] ; Cai Xin[22] ; Kong Wencui[23] ; Li Xiaoxue[24] ; Liang Fei[25] ;
机构： [1]Department of Pulmonary and Critical Care Medicine, Zhongshan Hospital, Fudan University, Shanghai, China [2]Department of Pulmonary and Critical Care Medicine, Shanghai Geriatrics Medical Center, Shanghai, China [3]Department of Oncology, The First Affiliated Hospital with Nanjing Medical University, Nanjing, China [4]Department of Oncology, The First Affiliated Hospital, Zhejiang University School of Medicine, Hangzhou, China [5]Department of Medical Oncology, The First Affiliated Hospital of Xi’an Jiaotong University, Xi’an, China [6]Department of Medical Oncology, Hunan Cancer Hospital/The Affiliated Cancer Hospital of Xiangya School of Medicine, Central South University, Changsha, China [7]Department of Oncology, The Second Hospital of Tianjin Medical University, Tianjin, China [8]Department of Thoracic Oncology, Ningbo No.2 Hospital, Ningbo, China [9]Department of Oncology, The Second Affiliated Hospital of Dalian Medical University, Dalian, China [10]Department of Pulmonary and Critical Care Medicine, The First Affiliated Hospital of Ningbo University, Ningbo, China [11]Department of Pulmonary and Critical Care Medicine, The First Affiliated Hospital of Guangxi Medical University, Nanning, China [12]Department of Lung Disease, Shenzhen Bao’an Traditional Chinese Medicine Hospital, Shenzhen, China [13]Department of Oncology, The Affiliated Hospital of Qingdao University, Qingdao, China [14]Department of Oncology, Jiangyin People’s Hospital, Wuxi, China [15]Department of Medical Oncology, Chinese PLA General Hospital, Beijing, China [16]Department of Oncology, Tangshan People’s Hospital, Tangshan, China [17]Department of Pulmonary and Critical Care Medicine, The First Affiliated Hospital of Wenzhou Medical University, Wenzhou, China [18]Department of Oncology, Cancer Hospital Chinese Academy of Medical Sciences, Beijing, China [19]Lung Cancer Center, West China Hospital of Sichuan University, Chengdu, China [20]Department of Pulmonary and Critical Care Medicine, The Third People’s Hospital of Cixi, Ningbo, China [21]Department of Pulmonary and Critical Care Medicine, Yiyang Central Hospital, Yiyang, China [22]Department of Oncology, The First Affiliated Hospital of Dalian Medical University, Dalian, China [23]Department of Pulmonary and Critical Care Medicine, The 900th Hospital of the Joint Logistic Support Force, People’s Liberation Army of China, Fuzhou, China [24]Department of Thoracic Surgery, Xuanwu Hospital, Capital Medical University, Beijing, China [25]Department of Biostatistics, Zhongshan Hospital, Fudan University, Shanghai, China
出处：
DOI： 10.1016/j.canlet.2025.217455
ISSN：

关键词： Pralsetinib Acquired RET fusion Resistance mechanisms Efficacy Allele frequency

摘要：
Pralsetinib demonstrated impressive improvement of survival in non-small cell lung cancer (NSCLC) patients harbored de novo RET fusion. However, the efficacy in patients with acquired RET fusion after resistance to EGFR/ALK-TKIs has only been reported on a case-by-case basis, and the strategy for overcoming the acquired RET fusion has not been fully investigated. This multicenter, real-world analysis enrolled 32 patients with unresectable NSCLC harbored acquired RET fusion after resistance to EGFR/ALK-TKIs in 23 centers across China from July 1st, 2018 to Nov 23rd, 2022. Epidemiological, clinical, genetic, and treatment data were collected. The primary outcome was time to treatment failure (TTF). Secondary outcomes were overall survival (OS), objective response rate (ORR), disease control rate (DCR) and toxicity. In real-world context, patients underwent pralsetinib-based treatment had a higher proportion of central nervous system metastasis. EGFR 19del was the predominant mutation type (62.5 %) prior to acquired RET fusion. CCDC6 was the commonest RET fusion partner (40.6 %). "Clonal RET fusion" (c-RET) and "subclonal RET fusion" (s-RET) were defined according to the RET fusion allele frequency. Patients with c-RET had higher proportions of undetected EGFR mutation and KIF5B-RET fusion. First-line pralsetinib-based therapy had notably superior median TTF when compared to their counterparts (8.03 versus 4.30 months, P = 0.016). Notably, patients with c-RET had a better prognosis than those with s-RET (median TTF: NR versus 5.67 months, P = 0.037, median OS: NR versus 9.83 months, P = 0.047). In conclusion, pralsetinib-based therapy may be a potential strategy to overcome acquired RET fusion after resistance to EGFR/ALK-TKIs.Copyright © 2025. Published by Elsevier B.V.

基金：
This study was supported by Science and Technology Commission of Shanghai Municipality (No. 20DZ2261200), National key R&D plan (No. 2020YFC2003700), and Shanghai Municipal Key Clinical Specialty (shslczdzk02201).
语种：
外文
WOS：
PubmedID：
中科院(CAS)分区：
出版当年[2025]版：
大类 | 1 区 医学
小类 | 2 区 肿瘤学
最新[2025]版：
大类 | 1 区 医学
小类 | 2 区 肿瘤学
JCR分区：
出版当年[2023]版：
Q1 ONCOLOGY
最新[2023]版：
Q1 ONCOLOGY

影响因子： 最新[2023版] 最新五年平均 出版当年[2023版] 出版当年五年平均 出版前一年[2022版]

第一作者：
第一作者机构： [1]Department of Pulmonary and Critical Care Medicine, Zhongshan Hospital, Fudan University, Shanghai, China
共同第一作者：
通讯作者：
通讯机构： [1]Department of Pulmonary and Critical Care Medicine, Zhongshan Hospital, Fudan University, Shanghai, China [2]Department of Pulmonary and Critical Care Medicine, Shanghai Geriatrics Medical Center, Shanghai, China
推荐引用方式(GB/T 7714)：
Tang Xinjun,Hu Jie,Guo Renhua,et al.RET-AREAL: A multi-center, real-world data analysis on the efficacy of pralsetinib in acquired RET fusion after resistance to EGFR/ALK-TKIs[J].Cancer Letters.2025,612:217455.doi:10.1016/j.canlet.2025.217455.
APA：
Tang Xinjun,Hu Jie,Guo Renhua,Wang Yina,Yao Yu...&Liang Fei.(2025).RET-AREAL: A multi-center, real-world data analysis on the efficacy of pralsetinib in acquired RET fusion after resistance to EGFR/ALK-TKIs.Cancer Letters,612,
MLA：
Tang Xinjun,et al."RET-AREAL: A multi-center, real-world data analysis on the efficacy of pralsetinib in acquired RET fusion after resistance to EGFR/ALK-TKIs".Cancer Letters 612.(2025):217455

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