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

	Apatinib vs Placebo in Patients With Locally Advanced or Metastatic, Radioactive Iodine-Refractory Differentiated Thyroid Cancer The REALITY Randomized Clinical Trial
	Lin, Yansong 23,24,25; Qin, Shukui 22; Li, Zhiyong 21; Yang, Hui 20; Fu, Wei 19; Li, Shaohua 18; Chen, Wenxin 17; Gao, Zairong 16; Miao, Weibing 15; Xu, Huiqin 14
刊名	JAMA ONCOLOGY
	2021-12-16
ISSN号	2374-2437
DOI	10.1001/jamaoncol.2021.6268
通讯作者	Lin, Yansong(linyansong1968@163.com) ; Qin, Shukui(qinsk@csco.org.cn)
英文摘要	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.
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
WOS关键词	DOUBLE-BLIND ; DISTANT METASTASES ; TYROSINE KINASE ; CARCINOMA ; LENVATINIB ; CABOZANTINIB ; MULTICENTER ; MANAGEMENT ; SORAFENIB ; INHIBITOR
WOS研究方向	Oncology
语种	英语
出版者	AMER MEDICAL ASSOC
WOS记录号	WOS:000731127300003
资助机构	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
内容类型	期刊论文
源URL	[http://ir.hfcas.ac.cn:8080/handle/334002/126958]
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.Jiangsu Inst Nucl Med, Dept Endocrinol, JiangYuan Hosp, Wuxi, Jiangsu, Peoples R China 2.Jiangsu Hengrui Pharmaceut Co Ltd, Shanghai, Peoples R China 3.Shanghai Jiao Tong Univ, Ruijin Hosp, Dept Nucl Med, Sch Med, Shanghai, Peoples R China 4.Sun Yat Sen Univ, Sun Yat Sen Mem Hosp, Dept Nucl Med, Guangzhou, Peoples R China 5.First Hosp Jilin Univ, Dept Thyroid Surg, Changchun, Peoples R China 6.Peking Univ Int Hosp, Dept Oncol, Beijing, Peoples R China 7.Jilin Univ, Dept Nucl Med, China Japan Union Hosp, Changchun, Peoples R China 8.Hebei Med Univ, Dept Otolaryngol Head & Neck Surg, Hosp 4, Shijiazhuang, Hebei, Peoples R China 9.First Hosp Jilin Univ, Dept Nucl Med, Changchun, Peoples R China 10.Shanxi Prov Canc Hosp, Dept Nucl Med, Taiyuan, 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).