Data Sheet 1_A Bayesian network meta-analysis: evaluating the efficacy and safety of targeted therapies in metastatic or advanced radioiodine-refractory differentiated thyroid cancer.docx

BackgroundApproximately 5%–10% of patients with differentiated thyroid cancer (DTC) develop resistance to radioactive iodine (RAI), leading to unsatisfactory survival rates. The optimal medication for advanced or metastatic RAI-resistant differentiated thyroid cancer (RAIR-DTC) remains unclear.
MethodsWe conducted a Bayesian network meta-analysis based on a systematic search of six electronic databases. The primary outcome was progression-free survival (PFS); secondary outcomes included overall survival (OS), objective response rate (ORR), and grade ≥3 adverse events (AEs). Hazard ratios (HRs) with 95% credible intervals (CrIs) were used for time-to-event outcomes, while odds ratios (ORs) with 95% CrIs were used for binary outcomes. A separate Bayesian network meta-analysis was performed for each endpoint.
ResultsOur study included 9 RCTs involving 1,760 patients with RAIR-DTC. Lenvatinib, anlotinib, apatinib, and cabozantinib all significantly improved PFS versus placebo (HRs: 3.85–5.36), with lenvatinib ranking first overall (SUCRA: 81.97%) and showing sustained benefit up to 24 months. Apatinib provided early PFS advantage but waning efficacy beyond 6–9 months. No treatment significantly improved OS, though apatinib consistently ranked highest for OS. Lenvatinib achieved the highest objective response rate (OR = 143.18; SUCRA: 82.09%). For grade ≥3 adverse events, no treatment differed significantly from placebo; however, apatinib ranked highest in safety (SUCRA = 93.16%).
ConclusionLenvatinib demonstrates the greatest benefit in both PFS and ORR among the evaluated TKIs for RAIR-DTC, suggesting it as a potential preferred first-line option. The time-dependent efficacy patterns of other TKIs warrant further investigation.
Systematic Review Registrationhttps://www.crd.york.ac.uk/prospero/display_record.php?ID=CRD420251089713, identifier CRD420251089713.

背景：约5%~10%的分化型甲状腺癌（differentiated thyroid cancer, DTC）患者会出现放射性碘（radioactive iodine, RAI）耐药，导致生存率不佳。目前晚期或转移性RAI难治性分化型甲状腺癌（RAI-resistant differentiated thyroid cancer, RAIR-DTC）的最优治疗药物仍不明确。
方法：本研究基于对6个电子数据库的系统检索，开展了贝叶斯网络meta分析。主要结局指标为无进展生存期（progression-free survival, PFS）；次要结局指标包括总生存期（overall survival, OS）、客观缓解率（objective response rate, ORR）及3级及以上不良事件（adverse events, AEs）。时间-事件结局采用带95%可信区间（95% credible intervals, CrIs）的风险比（hazard ratios, HRs）进行分析，二分类结局则采用带95% CrIs的比值比（odds ratios, ORs）进行分析。针对每个研究终点均开展了独立的贝叶斯网络meta分析。
结果：本研究共纳入9项随机对照试验（randomized controlled trial, RCT），涉及1760例RAIR-DTC患者。与安慰剂相比，仑伐替尼（lenvatinib）、安罗替尼（anlotinib）、阿帕替尼（apatinib）及卡博替尼（cabozantinib）均显著改善了PFS（HRs：3.85~5.36），其中仑伐替尼整体排名第一（排序累积排名曲线下面积（surface under the cumulative ranking curve, SUCRA）：81.97%），且其获益可持续至24个月。阿帕替尼早期可带来PFS优势，但在6~9个月后疗效逐渐减弱。所有治疗方案均未显著改善OS，不过阿帕替尼在OS方面始终排名最高。仑伐替尼的客观缓解率最高（OR=143.18；SUCRA：82.09%）。在3级及以上不良事件方面，所有治疗方案与安慰剂均无显著差异；但阿帕替尼的安全性排名最高（SUCRA=93.16%）。
结论：在本次评估的酪氨酸激酶抑制剂（tyrosine kinase inhibitors, TKIs）中，仑伐替尼在RAIR-DTC的PFS和ORR方面均展现出最优获益，提示其可作为潜在的首选一线治疗方案。其他TKIs的时间依赖性疗效模式有待进一步研究。
系统评价注册：https://www.crd.york.ac.uk/prospero/display_record.php?ID=CRD420251089713，注册编号为CRD420251089713。