Efficacy and safety of lenvatinib plus gefitinib in lenvatinibresistant hepatocellular carcinomas: a prospective, single-arm exploratory trial  

作　　者：Yaoping Shi Dan Cui Lei Xia Donghua Shi Guangxin Jin Siying Wang Yan Lin Xiaoyin Tang Jiachang Chi Tao Wang Meng Li Zicheng Lv Jiaojiao Zheng Qi Jia Wu Yang Zhen Sun Fan Yang Hao Feng Shengxian Yuan Weiping Zhou Wenxin Qin Rene Bernards Haojie Jin Bo Zhai 

机构地区：[1]Department of Interventional Oncology,State Key Laboratory of Systems Medicine for Cancer,Renji Hospital,Shanghai Jiao Tong University School of Medicine,Shanghai,PR China [2]Department of Liver Surgery,State Key Laboratory of Systems Medicine for Cancer,Renji Hospital,Shanghai Jiao Tong University School of Medicine,Shanghai,PR China [3]Shanghai Cancer Institute,State Key Laboratory of Systems Medicine for Cancer,Renji Hospital,Shanghai Jiao Tong University School of Medicine,Shanghai,PR China [4]Department of Pharmacy,Renji Hospital,Shanghai Jiao Tong University,Shanghai,PR China [5]The Third Department of Hepatic Surgery,Eastern Hepatobiliary Surgery Hospital,Third Affiliated Hospital,Naval Medical University,Shanghai,PR China [6]Division of Molecular Carcinogenesis,Oncode Institute,The Netherlands Cancer Institute,Amsterdam,The Netherlands

出　　处：《Signal Transduction and Targeted Therapy》2025年第1期314-320,共7页信号转导与靶向治疗(英文)

基　　金：supported by the National Natural Science Foundation(Nos.82222047,82073039,82330095,81502672,and 82070619);the Program of Shanghai Academic/Technology Research Leader(No.22XD1423100);the National Key Research and Development Program of China(2022YFC2804300);Shanghai Municipal Commission of Health and Family Planning(2022XD057);the Shanghai Committee of Science and Technology(23ZR1439000 and 22S11900500).

摘　　要：Lenvatinib,a multi-kinase inhibitor,has been approved asfirst-line treatment for advanced hepatocellular carcinoma(HCC),but its efficacy is limited.We have shown previously that lenvatinib and epidermal growth factor receptor tyrosine kinase inhibitor(EGFRTKI)combination therapy overcomes lenvatinib resistance in HCC with high level of EGFR expression(EGFR^(high)).We present here the results of a single-arm,open-label,exploratory study of lenvatinib plus the EGFR-TKI gefitinib for patients with HCC resistance to lenvatinib(NCT04642547;n=30).Only patients with EGFR^(high) HCC and progressive disease after lenvatinib treatment were recruited in the study.The most frequent adverse events of all grades were fatigue(27 patients;90%),followed by rash(25 patients;83.3%),diarrhea(24 patients;80%),and anorexia(12 patients;40%).Among 30 patients,9(30%)achieved a confirmed partial response and 14(46.7%)had stable disease according to mRECIST criteria.Based on RECIST1.1,5(16.7%)achieved a confirmed partial response and 18(60%)had stable disease.The estimated median progression free survival(PFS)and overall survival(OS)time were 4.4 months(95%CI:2.5 to 5.9)and13.7 months(95%CI:9.0 to NA),respectively.The objective response rate(ORR)of the patients in the present study compares very favorable to that seen for the two approved second line treatments for HCC(cabozantinib ORR of 4%;regorafenib ORR of 11%).Given that this combination was well-tolerated,a further clinical study of this combination is warranted.

关 键 词：GEFITINIB DIARRHEA treatment 

分 类 号：R73[医药卫生—肿瘤]