Department of Nuclear Medicine, Zhongshan Hospital, Fudan University, Shanghai, China.
Department of Nuclear Medicine, The First Affiliated Hospital of Zhengzhou University, Zhengzhou, China.
JAMA Netw Open. 2024 Nov 4;7(11):e2443407. doi: 10.1001/jamanetworkopen.2024.43407.
Radioactive iodine (131I or RAI) therapy has long been the standard of care for most patients with differentiated thyroid cancer (DTC) after primary surgery. However, no multicenter prospective studies have identified the optimal administered activity and stimulation method for RAI therapy in patients with intermediate-risk DTC.
To compare the efficacy and safety of recombinant human thyrotropin (SNA001) with thyroid hormone withdrawal (THW) plus 3.7 GBq RAI in patients with intermediate-risk DTC.
DESIGN, SETTING, AND PARTICIPANTS: This noninferiority, open-label, phase 3 randomized clinical trial was conducted at 19 sites in China from April 16, 2020, to September 9, 2021, with a follow-up period of 8 months. Patients aged 18 to 70 years with DTC who had undergone a total or near-total thyroidectomy and had no distant metastasis were enrolled in the trial. Statistical analysis followed the full analysis and per-protocol analysis sets and was performed between November 18, 2021, and April 18, 2022.
Patients were randomly assigned 1:1 to receive SNA001, 0.9 mg, intramuscular injection daily for 2 days or to undergo thyroid hormone withdrawal for 3 to 6 weeks.
The primary end point was the success rate after 6 to 8 months of RAI therapy. Success was defined as a negative diagnostic whole-body scan result and a stimulated thyroglobulin level less than 1.0 ng/mL.
A total of 307 patients (192 females [62.5%]; median [range] age, 40 [19-69] years) were randomized: 154 to the SNA001 group and 153 to the THW group. Baseline characteristics were evenly matched between the 2 groups. Noninferiority in the success rate of RAI therapy between groups was met, with success rates of 43.8% in the SNA001 group and 47.1% in the THW group (risk difference, -3.3; 95% CI, -14.8 to 8.3 percentage points). Forty-six patients (29.9%) in the SNA001 group reported adverse events compared with 90 (58.8%) in the THW group during RAI therapy (P < .001). No treatment-related adverse events leading to discontinuation and drug modification occurred in the SNA001 group.
This randomized clinical trial showed that SNA001 was noninferior to THW plus 3.7 GBq RAI in patients with predominantly intermediate-risk DTC. SNA001 also demonstrated a favorable safety profile compared with THW and had a lower incidence of adverse events.
Chinese Clinical Trial Registry Identifier: ChiCTR2100046907.
放射性碘（131I 或 RAI）治疗长期以来一直是大多数分化型甲状腺癌（DTC）患者在初次手术后的标准治疗方法。然而，尚无多中心前瞻性研究确定中间风险 DTC 患者接受 RAI 治疗的最佳给药剂量和刺激方法。
比较重组人促甲状腺激素（SNA001）与甲状腺激素停药（THW）加 3.7GBq RAI 在中间风险 DTC 患者中的疗效和安全性。
设计、地点和参与者：这是一项非劣效性、开放标签、3 期随机临床试验，于 2020 年 4 月 16 日至 2021 年 9 月 9 日在中国的 19 个地点进行，随访期为 8 个月。招募了年龄在 18 岁至 70 岁之间、接受过全甲状腺或近全甲状腺切除术且无远处转移的 DTC 患者。统计分析遵循全分析集和方案分析集，于 2021 年 11 月 18 日至 2022 年 4 月 18 日进行。
患者被随机分配 1:1 接受 SNA001，0.9mg，每日肌肉注射 2 天，或接受 THW 治疗 3 至 6 周。
主要终点是 6 至 8 个月 RAI 治疗后的成功率。成功定义为阴性诊断性全身扫描结果和刺激甲状腺球蛋白水平低于 1.0ng/mL。
共有 307 名患者（192 名女性[62.5%]；中位[范围]年龄为 40[19-69]岁）被随机分组：154 名患者接受 SNA001 治疗，153 名患者接受 THW 治疗。两组的基线特征均衡匹配。组间 RAI 治疗成功率无统计学差异，SNA001 组成功率为 43.8%，THW 组成功率为 47.1%（风险差，-3.3；95%CI，-14.8 至 8.3 个百分点）。在 RAI 治疗期间，SNA001 组有 46 名（29.9%）患者报告不良事件，而 THW 组有 90 名（58.8%）患者报告不良事件（P<0.001）。SNA001 组无与治疗相关的不良事件导致停药和药物调整。
这项随机临床试验表明，SNA001 在主要为中间风险的 DTC 患者中与 THW 加 3.7GBq RAI 相比不劣效。与 THW 相比，SNA001 也具有良好的安全性，不良事件发生率较低。
中国临床试验注册中心标识符：ChiCTR2100046907。
