白蛋白结合型紫杉醇一线治疗中国晚期胰腺癌的真实世界研究  

A real-world study of first-line albumin-bound paclitaxel in the treatment of advanced pancreatic cancer in China

作　　者：杜娟[1,2] 仇鑫[1] 倪嘉遥 王俏丽 同帆 沙慧子 朱雅慧 祁亮 蔡蔚 高超 魏晓为 陈敏斌 钱祝银 蔡茂怀[8] 陶敏 王彩莲[10] 郑国灿 蒋华 戴安伟 吴骏[13] 赵明宏[14] 李小琴[15] 陆斌[16] 王纯斌[17] 刘宝瑞[1] Du Juan;Qiu Xin;Ni Jiayao;Wang Qiaoli;Tong Fan;Sha Huizi;Zhu Yahui;Qi Liang;Cai Wei;Gao Chao;Wei Xiaowei;Chen Minbin;Qian Zhuyin;Cai Maohuai;Tao Min;Wang Cailian;Zheng Guocan;Jiang Hua;Dai Anwei;Wu Jun;Zhao Minghong;Li Xiaoqin;Lu Bin;Wang Chunbin;Liu Baorui(Department of Oncology,Nanjing Drum Tower Hospital,Affiliated Hospital of Medical School,Nanjing University,Nanjing 210008,China;Drum Tower Clinical College of Traditional Chinese and Western Medicine,Nanjing University of Chinese Medicine,Nanjing,210008,China;Department of Oncology,The First People's Hospital of Wujiang,Suzhou 215200,China;Department of Oncology,The Affiliated Hospital of Xuzhou Medical University,Xuzhou 221004,China;Department of Oncology,Nanjing First Hospital,Nanjing 210006,China;Department of Oncology,The First People's Hospital of Kunshan,Kunshan 215300,China;Department of Oncology,The Second Affiliated Hospital of Nanjing Medical University,Nanjing 210003,China;Department of Oncology,Yancheng Branch of Nanjing Drum Tower Hospital,Yancheng 224003,China;Department of Oncology,The First Affiliated Hospital of Soochow University,Suzhou 215006,China;Department of Oncology,Zhongda Hospital Southeast University,Nanjing 210009,China;Department of Oncology,The Second People's Hospital of Changzhou,Changzhou 213000,China;Department of Oncology,Traditional Chinese Medicine Hospital of Kunshan,Kunshan 215300,China;Department of Oncology,The First People's Hospital of Changzhou,Changzhou 213003,China;Department of Oncology,Jianhu County People's Hospital,Yancheng 224001,China;Department of Oncology,Affiliated Hospital of Jiangsu University,Zhenjiang 212001,China;Department of Oncology,The People's Hospital of Yangzhong,Yangzhong 212200,China;Department of Oncology,Yancheng Third People's Hospital,Yancheng 224000,China)

机构地区：[1]南京大学医学院附属鼓楼医院肿瘤科,南京210008 [2]南京中医药大学中西医结合鼓楼临床医学院,南京210008 [3]吴江第一人民医院肿瘤科,苏州215200 [4]徐州医科大学附属医院肿瘤科,徐州221004 [5]南京市第一医院肿瘤科,南京210006 [6]昆山市第一人民医院肿瘤科,昆山215300 [7]南京医科大学第二附属医院肿瘤科,南京210003 [8]南京鼓楼医院盐城分院肿瘤科,盐城224003 [9]苏州大学附属第一医院肿瘤科,苏州215006 [10]东南大学附属中大医院肿瘤科,南京210009 [11]常州市第二人民医院肿瘤科,常州213000 [12]昆山市中医院肿瘤科,昆山215300 [13]常州市第一人民医院肿瘤科,常州213003 [14]江苏省建湖县人民医院肿瘤科,盐城224001 [15]江苏大学附属医院肿瘤科,镇江212001 [16]扬中市人民医院肿瘤科,扬中212200 [17]盐城市第三人民医院肿瘤科,盐城224000

出　　处：《中华肿瘤杂志》2024年第11期1038-1048,共11页Chinese Journal of Oncology

基　　金：湖北陈孝平科技发展基金(CXPJJH11900001-2019101);“十四五”江苏省医学重点学科(ZDXK202233);南京市卫生科技发展专项资金项目(YKK20080)。

摘　　要：目的评价白蛋白结合型紫杉醇一线治疗中国晚期胰腺癌的临床疗效和安全性,并结合肿瘤组织二代高通量测序(NGS)检测等探索胰腺癌的预后相关分子。方法2018年12月至2020年12月在中国华东地区24家医院招募一线接受以白蛋白结合型紫杉醇为基础的治疗方案治疗的晚期胰腺癌患者229例。主要研究终点是总生存时间(OS)和治疗相关不良反应,次要研究终点是无进展生存时间(PFS)。对患者的手术切除或取活检的胰腺癌原发灶或转移灶组织标本进行NGS测序。结果229例患者的总体疾病控制率为79.9%,客观缓解率为36.3%。治疗期间常见的不良反应为贫血(159例)、白细胞减少(170例)、中性粒细胞减少(169例)、转氨酶升高(110例)和血小板减少(95例)等,其中3~4级中性粒细胞减少的发生率为12.2%(28/229)。中位随访时间为21.2个月,中位PFS为5.3个月,中位OS为11.2个月。其中70例局部晚期胰腺癌患者的中位PFS为7.4个月,中位OS为15.5个月;159例远处转移胰腺癌患者的中位PFS为3.9个月,中位OS为9.3个月。多因素Cox回归分析显示,临床分期(HR=1.47,95%CI:1.06~2.04)、原发肿瘤部位(HR=0.64,95%CI:0.48~0.86)、ECOG评分(HR=2.66,95%CI:1.53~4.65)和是否联合放疗(HR=0.65,95%CI:0.42~1.00)是接受以白蛋白结合型紫杉醇为基础治疗的晚期胰腺癌患者PFS的独立影响因素,原发肿瘤部位(HR=0.68,95%CI:0.48~0.95)、ECOG评分(HR=5.82,95%CI:3.14~10.82)和是否联合放疗(HR=0.58,95%CI:0.35~0.96)是接受以白蛋白结合型紫杉醇为基础治疗的晚期胰腺癌患者OS的独立影响因素。对87例有足量肿瘤组织标本的胰腺癌患者行NGS测序发现,中国晚期胰腺癌中基因突变频率居前4位的基因分别为KRAS(89.66%)、TP53(77.01%)、CDKN2A(32.18%)和SMAD4(21.84%)。CDKN2B、PTEN、FGF6和RBBP8基因突变增加晚期胰腺癌患者的死亡风险(均P<0.05)。结论在真实世界中,采用白蛋白结合型紫杉醇一线治疗中国�Objective To observe and evaluate the clinical efficacy and safety of albumin-bound paclitaxel as first-line treatment for patients with advanced pancreatic cancer in China,and to explore the prognosis-related molecules in pancreatic cancer based on next-generation sequencing(NGS)of tumor tissues.Methods From December 2018 to December 2020,patients with locally advanced or metastatic pancreatic cancer were recruited to accept albumin-bound paclitaxel as first-line treatment in the oncology departments of 24 hospitals in East China.The primary endpoints were overall survival(OS)and treatment related adverse events,and the secondary endpoint was progression-free survival(PFS).Adverse effects were graded using Common Terminology Criteria for Adverse Events 5.0(CTCAE 5.0).NGS sequencing on the primary or metastatic tissue samples of pancreatic cancer obtained through surgical resection or biopsy was performed.Results This study recruited 229 patients,including 70 patients with locally advanced pancreatic cancer(LAPC)and 159 patients with metastatic pancreatic cancer(mPC).The disease control rate was 79.9%and the objective response rate is 36.3%.The common adverse effects during treatment were anaemia(159 cases),leucopenia(170 cases),neutropenia(169 cases),increased aminotransferases(110 cases),and thrombocytopenia(95 cases),and the incidence of grade 3-4 neutropenia is 12.2%(28/229).The median follow-up time was 21.2 months(95%CI:18.5-23.1 months).The median PFS(mPFS)was 5.3 months(95%CI:4.37-4.07 months)and the median OS(mOS)was 11.2 months(95%CI:9.5-12.9 months).The mPFS of patients with LAPC was 7.4 months(95%CI:6.6-11.2 months),and their mOS was 15.5 months(95%CI:12.6-NA months).The mPFS of patients with mPC was 3.9 months(95%CI:3.4-5.1 months),and their mOS was 9.3 months(95%CI:8.0-10.8 months).Multivariate Cox regression analysis showed that clinical stage(HR=1.47,95%CI:1.06-2.04),primary tumor site(HR=0.64,95%CI:0.48-0.86),Eastern Cooperative Oncology Group Performance Status(ECOG PS)score(HR=2.66,95%CI:1.53-4

关 键 词：胰腺肿瘤 白蛋白结合型紫杉醇 吉西他滨 一线化疗 真实世界研究 

分 类 号：R735.9[医药卫生—肿瘤]