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

Department of Nuclear Medicine, Peking Union Medical College Hospital, Beijing, China. Beijing Key Laboratory of Molecular Targeted Diagnosis and Therapy in Nuclear Medicine, Beijing, China. State Key Laboratory of Complex Severe and Rare Diseases, Peking Union Medical College Hospital, Chinese Academy of Medical Science and Peking Union Medical College, Beijing, China. Department of Medical Oncology, Cancer Center of Bayi Hospital, Nanjing Chinese Medicine University, Nanjing, China. Department of Nuclear Medicine, The Affiliated Hospital of Xuzhou Medical University, Xuzhou, China. Department of Nuclear Medicine, The Affiliated Cancer Hospital of Zhengzhou University, Zhengzhou, China. Department of Nuclear Medicine, The Affiliated Hospital of Guilin Medical University, Guilin, China. Department of Nuclear Medicine, Nanjing First Hospital, Nanjing, China. Department of Nuclear Medicine, Fujian Provincial Hospital, Fuzhou, China. Department of Nuclear Medicine, Union Hospital, Tongji Medical College, Huazhong University of Science and Technology, Wuhan, China. Department of Nuclear Medicine, Fujian Provincial Key Laboratory of Precision Medicine for Cancer, The First Affiliated Hospital of Fujian Medical University, Fuzhou, China. Department of Nuclear Medicine, The First Affiliated Hospital of Anhui Medical University, Hefei, China. Department of Nuclear Medicine, The First Affiliated Hospital of Nanchang University, Nanchang, China. Department of Nuclear Medicine, The Fourth Hospital of Hebei Medical University, Shijiazhuang, China. Department of Endocrinology, JiangYuan Hospital Affiliated to Jiangsu Institute of Nuclear Medicine, Wuxi, China. Department of Nuclear Medicine, Cancer Hospital of the University of Chinese Academy of Sciences (Zhejiang Cancer Hospital), Key Laboratory of Head & Neck Cancer Translational Research of Zhejiang Province, Hangzhou, China. Department of Nuclear Medicine, Shanxi Provincial Cancer Hospital, Taiyuan, China. Department of Nuclear Medicine, The First Hospital of Jilin University, Changchun, China. Department of Otolaryngology-Head and Neck Surgery, The Fourth Hospital of Hebei Medical University, Shijiazhuang, China. Department of Nuclear Medicine, China-Japan Union Hospital of Jilin University, Changchun, China. Department of Oncology, Peking University International Hospital, Beijing, China. Department of Thyroid Surgery, The First Hospital of Jilin University, Changchun, China. Department of Nuclear Medicine, Sun Yat-sen Memorial Hospital, Sun Yat-sen University, Guangzhou, Guangdong, China. Department of Nuclear Medicine, Ruijin Hospital, Shanghai Jiao Tong University School of Medicine, Shanghai, China. Jiangsu Hengrui Pharmaceuticals Co, Ltd, Shanghai, China.

JAMA oncology. 2022;(2):242-250
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Abstract

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. TRIAL REGISTRATION ClinicalTrials.gov Identifier: NCT03048877.

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