Apatinib vs Placebo in Patients With Locally Advanced or Metastatic, Radioactive Iodine-Refractory Differentiated Thyroid Cancer The REALITY Randomized Clinical Trial

doi:10.1001/jamaoncol.2021.6268

HFCAS OpenIR

	Apatinib vs Placebo in Patients With Locally Advanced or Metastatic, Radioactive Iodine-Refractory Differentiated Thyroid Cancer The REALITY Randomized Clinical Trial
	Lin, Yansong 1,2,3; Qin, Shukui 4; Li, Zhiyong 5; Yang, Hui 6; Fu, Wei 7; Li, Shaohua 8; Chen, Wenxin 9; Gao, Zairong 10; Miao, Weibing 11; Xu, Huiqin 12; Zhang, Qing 13; Zhao, Xinming 14; Bao, Jiandong 15; Li, Linfa 16; Ren, Yuan 17; Lin, Chenghe 18; Jing, Shanghua 19; Ma, Qingjie 20; Liang, Jun 21; Chen, Guang 22; Zhang, Hong 23; Zhang, Yifan 24; Zhou, Xianfeng 25; Sang, Yaxiong 25; Hou, Zhiguo 25
	2021-12-16
发表期刊	JAMA ONCOLOGY
ISSN	2374-2437
通讯作者	Lin, Yansong(linyansong1968@163.com) ; Qin, Shukui(qinsk@csco.org.cn)
摘要	IMPORTANCE Patients with radioactive iodine-refractory differentiated thyroid cancer (RAIR-DTC) have a poor prognosis and limited treatment options. OBJECTIVE To assess the efficacy and safety of apatinib, a highly selective vascular endothelial growth factor (VEGFR-2) inhibitor, in patients with progressive locally advanced or metastatic RAIR-DTC. DESIGN, SETTING, AND PARTICIPANTS This randomized, double-blind, placebo-controlled, phase 3 trial (Efficacy of Apatinib in Radioactive Iodine-refractory Differentiated Thyroid Cancer [REALITY]) was conducted in 92 patients with progressive locally advanced or metastatic RAIR-DTC between February 17, 2017, and March 2, 2020, at 21 sites within China, and the data cutoff date for this analysis was March 25, 2020. INTERVENTIONS Patients were randomly assigned (1:1) to apatinib, 500 mg/d, or placebo. Patients who developed progression while receiving placebo were allowed to cross over to apatinib. MAIN OUTCOMES AND MEASURES The primary end point was investigator-assessed progression-free survival (PFS). Secondary end points included overall survival, objective response rate (ORR), disease control rate (DCR), duration of response, time to objective response, and safety. Intention-to-treat analyses were performed to evaluate efficacy. RESULTS Of the 92 patients included in the trial, 56 were women (60.9%); mean (SD) age at baseline was 55.7 (10.6) years. Patients were randomized to the apatinib (n = 46) or placebo (n = 46) group. The median follow-up duration was 18.1 (IQR, 12.7-22.2) months. The median PFS was 22.2 (95% CI, 10.91-not reached) months for apatinib vs 4.5 (95% CI, 1.94-9.17) months for placebo (hazard ratio, 0.26; 95% CI, 0.14-0.47; P < .001). The confirmed ORR was 54.3% (95% CI, 39.0%-69.1%) and the DCR was 95.7% (95% CI, 85.2%-99.5%) in the apatinib group vs an ORR of 2.2% (95% CI, 0.1%-11.5%) and DCR of 58.7% (95% CI, 43.2%-73.0%) in the placebo group. The median overall survival was not reached for apatinib (95% CI, 26.25-not reached) and was 29.9 months (95% CI, 18.96-not reached) for placebo (hazard ratio, 0.42; 95% CI, 0.18-0.97; P = .04). The most common grade 3 or higher-level treatment-related adverse events in the apatinib group were hypertension (16 [34.8%]), hand-foot syndrome (8 [17.4%]), proteinuria (7 [15.2%]), and diarrhea (7 [15.2%])-none of which occurred in the placebo group. CONCLUSIONS AND RELEVANCE The REALITY trial met its primary end point of PFS at the prespecified interim analysis. Apatinib showed significant clinical benefits in both prolonged PFS and overall survival with a manageable safety profile in patients with progressive locally advanced or metastatic RAIR-DTC.
DOI	10.1001/jamaoncol.2021.6268
关键词[WOS]	DOUBLE-BLIND ; DISTANT METASTASES ; TYROSINE KINASE ; CARCINOMA ; LENVATINIB ; CABOZANTINIB ; MULTICENTER ; MANAGEMENT ; SORAFENIB ; INHIBITOR
收录类别	SCI
语种	英语
资助项目	National Natural Science Foundation of China[81771875] ; Project on Inter-Governmental International Scientific and Technological Innovation Cooperation in the National Key Projects of Research and Development Plan[2019YFE0106400] ; Jiangsu Hengrui Pharmaceuticals Co Ltd
项目资助者	National Natural Science Foundation of China ; Project on Inter-Governmental International Scientific and Technological Innovation Cooperation in the National Key Projects of Research and Development Plan ; Jiangsu Hengrui Pharmaceuticals Co Ltd
WOS研究方向	Oncology
WOS类目	Oncology
WOS记录号	WOS:000731127300003
出版者	AMER MEDICAL ASSOC
引用统计	被引频次：49[WOS] [WOS记录] [WOS相关记录]
文献类型	期刊论文
条目标识符	http://ir.hfcas.ac.cn:8080/handle/334002/126959
专题	中国科学院合肥物质科学研究院
通讯作者	Lin, Yansong; Qin, Shukui
作者单位	1.Peking Union Med Coll Hosp, Dept Nucl Med, Beijing, Peoples R China 2.Beijing Key Lab Mol Targeted Diag & Therapy Nucl, Beijing, Peoples R China 3.Chinese Acad Med Sci & Peking Union Med Coll, Peking Union Med Coll Hosp, State Key Lab Complex Severe & Rare Dis, Beijing, Peoples R China 4.Nanjing Chinese Med Univ, Canc Ctr Bayi Hosp, Dept Med Oncol, Nanjing, Peoples R China 5.Xuzhou Med Univ, Dept Nucl Med, Affiliated Hosp, Xuzhou, Jiangsu, Peoples R China 6.Zhengzhou Univ, Dept Nucl Med, Affiliated Canc Hosp, Zhengzhou, Peoples R China 7.Guilin Med Univ, Dept Nucl Med, Affiliated Hosp, Guilin, Peoples R China 8.Nanjing First Hosp, Dept Nucl Med, Nanjing, Peoples R China 9.Fujian Prov Hosp, Dept Nucl Med, Fuzhou, Peoples R China 10.Huazhong Univ Sci & Technol, Union Hosp, Tongji Med Coll, Dept Nucl Med, Wuhan, Peoples R China 11.Fujian Med Univ, Dept Nucl Med, Fujian Prov Key Lab Precis Med Canc, Affiliated Hosp 1, Fuzhou, Peoples R China 12.Anhui Med Univ, Dept Nucl Med, Affiliated Hosp 1, Hefei, Peoples R China 13.Nanchang Univ, Dept Nucl Med, Affiliated Hosp 1, Nanchang, Jiangxi, Peoples R China 14.Hebei Med Univ, Dept Nucl Med, Hosp 4, Shijiazhuang, Hebei, Peoples R China 15.Jiangsu Inst Nucl Med, Dept Endocrinol, JiangYuan Hosp, Wuxi, Jiangsu, Peoples R China 16.Univ Chinese Acad Sci, Dept Nucl Med, Key Lab Head & Neck Canc Translat Res Zhejiang Pr, Canc Hosp,Zhejiang Canc Hosp, Hangzhou, Peoples R China 17.Shanxi Prov Canc Hosp, Dept Nucl Med, Taiyuan, Peoples R China 18.First Hosp Jilin Univ, Dept Nucl Med, Changchun, Peoples R China 19.Hebei Med Univ, Dept Otolaryngol Head & Neck Surg, Hosp 4, Shijiazhuang, Hebei, Peoples R China 20.Jilin Univ, Dept Nucl Med, China Japan Union Hosp, Changchun, Peoples R China 21.Peking Univ Int Hosp, Dept Oncol, Beijing, Peoples R China 22.First Hosp Jilin Univ, Dept Thyroid Surg, Changchun, Peoples R China 23.Sun Yat Sen Univ, Sun Yat Sen Mem Hosp, Dept Nucl Med, Guangzhou, Peoples R China 24.Shanghai Jiao Tong Univ, Ruijin Hosp, Dept Nucl Med, Sch Med, Shanghai, Peoples R China 25.Jiangsu Hengrui Pharmaceut Co Ltd, Shanghai, Peoples R China
推荐引用方式 GB/T 7714	Lin, Yansong,Qin, Shukui,Li, Zhiyong,et al. Apatinib vs Placebo in Patients With Locally Advanced or Metastatic, Radioactive Iodine-Refractory Differentiated Thyroid Cancer The REALITY Randomized Clinical Trial[J]. JAMA ONCOLOGY,2021.
APA	Lin, Yansong.,Qin, Shukui.,Li, Zhiyong.,Yang, Hui.,Fu, Wei.,...&Hou, Zhiguo.(2021).Apatinib vs Placebo in Patients With Locally Advanced or Metastatic, Radioactive Iodine-Refractory Differentiated Thyroid Cancer The REALITY Randomized Clinical Trial.JAMA ONCOLOGY.
MLA	Lin, Yansong,et al."Apatinib vs Placebo in Patients With Locally Advanced or Metastatic, Radioactive Iodine-Refractory Differentiated Thyroid Cancer The REALITY Randomized Clinical Trial".JAMA ONCOLOGY (2021).