Phase Ⅱ study of apatinib in combination with oral vinorelbine in heavily pretreated HER2-negative metastatic breast cancer and clinical implications of monitoring ctDNA  

作　　者：Anjie Zhu Peng Yuan Nanlin Hu Mingzhou Li Wenmiao Wang Xue Wang Jian Yue Jiayu Wang Yang Luo Fei Ma Pin Zhang Qing Li Binghe Xu Shanbo Cao Giuseppe Lippi Yoichi Naito Mohammed A.Osman Gustavo N.Marta Gianluca Franceschini Armando Orlandi 

机构地区：[1]Department of Medical Oncology,National Cancer Center/National Clinical Research Center for Cancer/Cancer Hospital,Chinese Academy of Medical Sciences and Peking Union Medical College,Beijing 100021,China [2]Key Laboratory of Carcinogenesis and Translational Research(Ministry of Education/Beijing),Department of Breast,Oncology,Peking University Cancer Hospital&Institute,Beijing 100142,China [3]Department of VIP Medical Services,National Cancer Center/National Clinical Research Center for Cancer/Cancer Hospital,Chinese Academy of Medical Sciences and Peking Union Medical College,Beijing 100021,China [4]Department of Pathology,National Cancer Center/National Clinical Research Center for Cancer/Cancer Hospital,Chinese Academy of Medical Sciences and Peking Union Medical College,Beijing 100021,China [5]Acorn Med Biotechnology Co.,Ltd.,Beijing 101102,China [6]Section of Clinical Biochemistry,University Hospital of Verona,Verona,Verona 37100,Italy [7]Department of Breast and Medical Oncology,National Cancer Center Hospital East,Kashiwa 277-8577,Japan [8]Clinical Oncology,General Organization for Teaching Hospitals,Cairo 11435,Egypt [9]Department of Radiation Oncology,Hospital Sírio-Libanês,Sao Paulo 01308-050,Brazil [10]Multidisciplinary Breast Center,Fondazione Policlinico Universitario A.Gemelli IRCCS,UniversitàCattolica del Sacro Cuore,Rome 00176,Italy [11]Unit of Medical Oncology,Fondazione Policlinico Universitario A.Gemelli IRCCS,Roma 00176,Italy

出　　处：《Cancer Biology & Medicine》2021年第3期875-887,共13页癌症生物学与医学（英文版）

基　　金：funded by the National Natural Science Foundation of China(Grant No.81472753 and 81672634)。

摘　　要：Objective:Apatinib is an oral TKI targeting VEGFR-2.Single-agent apatinib treatment has been shown to produce an objective response in patients with pretreated m BC.Oral vinorelbine also holds promise as a treatment of choice in patients with m BC.This study aimed to investigate the efficacy and safety of the oral vinorelbine-apatinib combination in patients with pretreated m BC.In addition,we detected gene variants in ct DNA to explore the therapeutic implications.Methods:This study enrolled patients with HER2-negative m BC who were pretreated with anthracycline/taxanes.Patients were treated with apatinib at 500 mg/425 mg daily plus oral vinorelbine 60 mg/m2 on days 1,8,and 15 of every cycle(3 weeks).The primary endpoint was PFS.The secondary endpoints were ORR,CBR,OS,and safety.Patients eligible for ct DNA detection were evaluated before and during treatment.Results:Forty patients were enrolled.The median PFS was 5.2 months(95%CI,3.4–7.0 months),and the median OS was 17.4 months(95%CI,8.0–27.0 months).The ORR was 17.1%(6/35),and the CBR was 45.7%(16/35).The most common AEs included gastrointestinal reaction,myelosuppression,and hypertension.In 20 patients,ct DNA was detected at baseline and during treatment.A significant difference was found in PFS for undetected vs.detected baseline ct DNA(13.9 months vs.3.6 months,P=0.018).Conclusions:All-oral therapy with apatinib plus vinorelbine displayed objective efficacy in patients with heavily pretreated HER2-negative m BC,with acceptable and manageable toxicity profiles.Patients with no gene variant detected and lower variant allele frequencies in ct DNA at baseline showed longer PFS.

关 键 词：Metastatic breast cancer apatinib oral vinorelbine ct DNA 

分 类 号：R737.9[医药卫生—肿瘤]