Effect of Fruquintinib vs Placebo on Overall Survival in Patients With Previously Treated Metastatic Colorectal Cancer: The FRESCO Randomized Clinical Trial.
机构：[1]Department of Medical Oncology, Tongji University Shanghai East Hospital, Shanghai, China[2]Department of Medical Oncology, Shanghai Medical College, Fudan University Shanghai Cancer Center, Shanghai, China[3]Department of Medical Oncology, Nanjing Chinese Medicine University–Affiliated Bayi Hospital, Nanjing, China[4]Department of Medical Oncology, Sun Yat-sen University Cancer Center, State Key Laboratory of Oncology in South China, Guangzhou, China[5]Collaborative Innovation Center for Cancer Medicine, Guangzhou, China[6]Department of Medical Oncology, Beijing University Cancer Center, Beijing, China[7]Department of Medical Oncology, 307th Hospital of Chinese People's Liberation Army, The Affiliated Hospital of Military Medical Sciences, Beijing, China[8]Department of Medical Oncology, Harbin Medical University Cancer Hospital, Harbin, China[9]Department of Medical Oncology, Nantong Cancer Hospital, Nantong, China[10]Department of Medical Oncology, The Sixth Affiliated Hospital of Sun Yat-sen University, Guangzhou, China中山大学附属第六医院[11]Department of Medical Oncology, The Second Hospital of Anhui Medical University, Hefei, China[12]Department of Medical Oncology, Zhejiang Cancer Hospital, Hangzhou, China浙江省肿瘤医院[13]Department of Medical Oncology, Sir RunRun Shaw Hospital, College of Medicine, Zhejiang University, Hangzhou, China[14]Department of Medical Oncology, Jiangsu Provincial Hospital, Nanjing, China[15]Department of Medical Oncology, The Second Affiliated Hospital of Zhejiang University School of Medicine, Hangzhou, China[16]Department of Medical Oncology, Peking Union Medical College Hospital, Beijing, China[17]Department of Medical Oncology, The First Affiliated Hospital of Zhejiang University School of Medicine, Hangzhou, China浙江大学医学院附属第一医院[18]Department of Medical Oncology, Fudan University Zhongshan Hospital, Shanghai Medical College, Shanghai, China[19]Department of Medical Oncology, Guangdong General Hospital, Guangzhou, China广东省人民医院[20]Department of Medical Oncology, The First People's Hospital of Changzhou, Changzhou, China[21]Department of Medical Oncology, Jilin Province Cancer Hospital, Changchun, China[22]Department of Medical Oncology, Shanghai Jiaotong University Affiliated First People’s Hospital, Shanghai, China[23]Department of Medical Oncology, The First Hospital of Jilin University, Changchun, China[24]Department of Medical Oncology, Xuzhou Central Hospital, Xuzhou, China[25]Department of Medical Oncology, The Affiliated Hospital of Medical College Qingdao University, Qingdao, China[26]Department of Medical Oncology, The Third Xiangya Hospital of Central South University, Changsha, China[27]Department of Medical Oncology, LiuzhouWorker's Hospital, Liuzhou, China[28]Department of Medical Oncology, Shanghai Changzheng Hospital, The Second Military Medical University, Shanghai, China[29]Department of Medical Oncology, Peking University Shenzhen Hospital, Beijing University, Shenzhen, China北京大学深圳医院深圳市康宁医院深圳医学信息中心[30]Department of Medical Oncology, The Affiliated Hospital of Xuzhou Medical College, Xuzhou Medical College, Xuzhou, China[31]Hutchison MediPharma Ltd, Shanghai, China
Patients with metastatic colorectal cancer (CRC) have limited effective and tolerable treatment options.
To evaluate the efficacy and safety of oral fruquintinib, a vascular endothelial growth factor receptor (VEGFR) inhibitor, as third-line or later therapy in patients with metastatic CRC.
FRESCO (Fruquintinib Efficacy and Safety in 3+ Line Colorectal Cancer Patients) was a randomized, double-blind, placebo-controlled, multicenter (28 hospitals in China), phase 3 clinical trial. From December 2014 to May 2016, screening took place among 519 patients aged 18 to 75 years who had metastatic CRC that progressed after at least 2 lines of chemotherapy but had not received VEGFR inhibitor therapy; 416 met the eligibility criteria and were stratified by prior anti-VEGF therapy and K-ras status. The final date of follow-up was January 17, 2017.
Patients were randomized in a 2:1 ratio to receive either fruquintinib, 5 mg (n = 278) or placebo (n = 138) orally, once daily for 21 days, followed by 7 days off in 28-day cycles, until disease progression, intolerable toxicity, or study withdrawal.
The primary end point was overall survival. Key secondary efficacy endpoints were progression-free survival (time from randomization to disease progression or death), objective response rate (confirmed complete or partial response), and disease control rate (complete or partial response, or stable disease recorded ≥8 weeks postrandomization). Duration of response was also assessed. Safety outcomes included treatment-emergent adverse events.
Of the 416 randomized patients (mean age, 54.6 years; 161 [38.7%] women), 404 (97.1%) completed the trial. Median overall survival was significantly prolonged with fruquintinib compared with placebo (9.3 months [95% CI, 8.2-10.5] vs 6.6 months [95% CI, 5.9-8.1]); hazard ratio (HR) for death, 0.65 (95% CI, 0.51-0.83; P < .001). Median progression-free survival was also significantly increased with fruquintinib (3.7 months [95% CI, 3.7-4.6] vs 1.8 months [95% CI, 1.8-1.8] months); HR for progression or death, 0.26 (95% CI, 0.21 to 0.34; P < .001). Grades 3 and 4 treatment-emergent adverse events occurred in 61.2% (170) of patients who received fruquintinib and 19.7% (27) who received placebo. Serious adverse events were reported by 15.5% (43) of patients in the fruquintinib group and 5.8% (8) in the placebo group, with 14.4% (40) of fruquintinib-treated and 5.1% (7) of placebo-treated patients requiring hospitalization.
Among Chinese patients with metastatic CRC who had tumor progression following at least 2 prior chemotherapy regimens, oral fruquintinib compared with placebo resulted in a statistically significant increase in overall survival. Further research is needed to assess efficacy outside of China.
ClinicalTrials.gov Identifier: NCT02314819.
基金：
This study was sponsored
by Hutchison MediPharma, and was supported
by grants from the Ministry of Science and
Technology of the People's Republic of China
(2013ZX09101105) and the Science and Technology
Development Fund of Pudong Shanghai China
(PKJ2014-S01).
第一作者机构：[1]Department of Medical Oncology, Tongji University Shanghai East Hospital, Shanghai, China[2]Department of Medical Oncology, Shanghai Medical College, Fudan University Shanghai Cancer Center, Shanghai, China
共同第一作者：
通讯作者：
通讯机构：[3]Department of Medical Oncology, Nanjing Chinese Medicine University–Affiliated Bayi Hospital, Nanjing, China[*1]Department of Medical Oncology, Nanjing Chinese Medicine University Affiliated Bayi Hospital, No. 34, 34 Biao, Yanggongjing, Nanjing, Jiangsu, 210001, China
推荐引用方式(GB/T 7714)：
Jin Li,Shukui Qin,Rui-Hua Xu,et al.Effect of Fruquintinib vs Placebo on Overall Survival in Patients With Previously Treated Metastatic Colorectal Cancer: The FRESCO Randomized Clinical Trial.[J].JAMA.2018,319(24):2486-2496.doi:10.1001/jama.2018.7855.
APA：
Jin Li,Shukui Qin,Rui-Hua Xu,Lin Shen,Jianming Xu...&Weiguo Su.(2018).Effect of Fruquintinib vs Placebo on Overall Survival in Patients With Previously Treated Metastatic Colorectal Cancer: The FRESCO Randomized Clinical Trial..JAMA,319,(24)
MLA：
Jin Li,et al."Effect of Fruquintinib vs Placebo on Overall Survival in Patients With Previously Treated Metastatic Colorectal Cancer: The FRESCO Randomized Clinical Trial.".JAMA 319..24(2018):2486-2496
