CMAB009 plus irinotecan versus irinotecan-only as second-line treatment after fluoropyrimidine and oxaliplatin failure in KRAS wild-type metastatic colorectal cancer patients:promising findings from a prospective,open-label,randomized,phase III trial  

作　　者：Yuankai Shi Jin Li Jianming Xu Yan Sun Liwei Wang Ying Cheng Wei Liu Guoping Sun Yigui Chen Li Bai Yiping Zhang Xiaohui He Yi Luo Zhehai Wang Yunpeng Liu Qiang Yao Yuhong Li Shukui Qin Xiaohua Hu Feng Bi Rongsheng Zheng Xuenong Ouyang 

机构地区：[1]Department of Medical Oncology,Beijing Key Laboratory of Clinical Study On Anticancer Molecular Targeted Drugs,National Cancer Center/National Clinical Research Center for Cancer/Cancer Hospital,Chinese Academy of Medical Sciences and Peking Union Medical College,Beijing 100021,P.R.China [2]Fudan University Shanghai Cancer Center,Shanghai 200032,P.R.China [3]The Affiliated Hospital of Military Medical Sciences,Beijing 100071,P.R.China [4]Shanghai General Hospital,Shanghai 200080,P.R.China [5]Jilin Cancer Hospital,Changchun 130012,Jilin,P.R.China [6]Tumor Hospital of Hebei Province,Shijiazhuang 050011,Hebei,P.R.China [7]The First Affiliated Hospital of Anhui Medical University,Hefei 230022,Anhui,P.R.China [8]Fujian Provincial Cancer Hospital,Fuzhou 350014,Fujian,P.R.China [9]Chinese People’s Liberation Army General Hospital,Beijing 100853,P.R.China [10]Zhejiang Cancer Hospital,Hangzhou 310022,Zhejiang,P.R.China [11]Hunan Cancer Hospital,Changsha 410013,Hunan,P.R.China [12]Shandong Cancer Hospital,Jinan 250117,Shandong,P.R.China [13]The First Hospital of China Medical University,Shenyang 110001,Liaoning,P.R.China [14]Tianjin People’s Hospital,Tianjin 300121,P.R.China [15]Sun Yat-sen University Cancer Center,State Key Laboratory of Oncology in South China,Collaborative Innovation Center of Cancer Medicine,Guangzhou 510060,Guangdong,P.R.China [16]Chinese People’s Liberation Army Bayi Hospital,Nanjing 210002,Jiangsu,P.R.China [17]The Guangxi Zhuang Autonomous Region Tumor Hospital,Nanning 530021,Guangxi,P.R.China [18]West China Hospital,Chengdu 610041,Sichuan,P.R.China [19]First Affiliated Hospital of Bengbu Medical College,Bengbu 233004,Anhui,P.R.China [20]Fuzhou People’s Liberation Army General Hospital,Fuzhou 350025,Fujian,P.R.China

出　　处：《Cancer Communications》2019年第1期258-270,共13页癌症通讯（英文）

基　　金：Shanghai Zhangjiang Biotechnology Co.,Ltd.initiated and support this study;This work was also supported by the Chinese National Major Project for New Drug Innovation(2012ZX09101103,2013ZX09101002-001-001,and 2008ZX09312)

摘　　要：Background:The 5-fluorouracil/leucovorin plus oxaliplatin(FOLFOX)regimen is the standard first-line treatment for metastatic colorectal cancer(mCRC),however,the optimal second-line regimen for KRAS wild-type mCRC patients is still investigational.In this study,we aimed to determine the clinical efficacy and safety of CMAB009 plus irinotecan compared to irinotecan-only as a second-line regimen for treating KRAS wild-type mCRC patients.Methods:Patients with KRAS wild-type mCRC who had previously failed to respond to FOLFOX treatment were ran-domly assigned in a 2:1 ratio,to receive CMAB009 plus irinotecan or irinotecan-only.Patients receiving irinotecan-only were permitted to switch to CMAB009 therapy on disease progression and were grouped as the sequential-CMAB009 arm.The primary endpoints were overall response rate(ORR)and median progression-free survival(PFS).The second-ary endpoints were median overall survival(OS),disease control rate(DCR),clinical benefit rate(CBR),and duration of response(DOR).Results:The CMAB009 plus irinotecan arm demonstrated significantly improved ORR(33.2%vs.12.8%;P<0.001)and longer median PFS(169 days vs.95 days;P<0.001)as compared to the irinotecan-only arm.Patients receiv-ing CMAB009 plus irinotecan also demonstrated improved DCR(80.1%vs.65.2%,P<0.001),CBR(30.0%vs.14.6%,P<0.001),and DOR(210 days vs.109 days;P<0.001)as compared to irinotecan-only.However,patients treated with CMAB009 had an increased risk of skin rash(66.9%vs.5.5%,P<0.001)and paronychia(9.8%vs.0.0%,P<0.001).Anti-drug antibodies(ADA)were detected in 3.6%of patients,and only 0.9%of patients who received CMAB009 experienced hypersensitivity reactions.In patients receiving sequential-CMAB009 therapy after failure with irinotecan,their median PFS was 84 days (95% CI 65 to 113 days). The median OS was 425 days for patients receiving CMAB009 plus irinotecan and 401 days for those with sequential-CMAB009 (P = 0.940). Conclusions: Treatment with CMAB009 plus irinotecan was found to be a superior second-line regimen in com-par

关 键 词：CMAB009 Cetuximab IRINOTECAN SECOND-LINE mCRC EGFR KRAS Immunogenicity FLUOROPYRIMIDINE Oxaliplatin failure 

分 类 号：R73[医药卫生—肿瘤]