酪氨酸激酶抑制剂在难治性甲状腺癌治疗中的疗效与安全性: 一项网络Meta分析

doi:10.5246/jcps.2025.05.036

中国药学(英文版) ›› 2025, Vol. 34 ›› Issue (5): 470-484.DOI: 10.5246/jcps.2025.05.036

酪氨酸激酶抑制剂在难治性甲状腺癌治疗中的疗效与安全性: 一项网络Meta分析

朱祎潇¹, 张丽蓉¹, 吴文华¹, 林慧婷¹, 魏晓霞²^,^*()

^1. 福建医科大学药学院, 福建省立医院, 福州大学附属省立医院, 福建福州 350001
^2. 福建医科大学省立临床医学院药学部, 福州大学附属省立医院, 福建医科大学药学院, 福建福州 350001

收稿日期:2024-12-24 修回日期:2025-02-08 接受日期:2025-02-18 出版日期:2025-06-02 发布日期:2025-06-01
通讯作者: 魏晓霞

Efficacy and safety of tyrosine kinase inhibitors in treating refractory thyroid cancer: A network meta-analysis

Yixiao Zhu¹, Lirong Zhang¹, Wenhua Wu¹, Huiting Lin¹, Xiaoxia Wei²^,^*()

¹ School of Pharmacy, Fujian Medical University; Fujian Provincial Hospital Fuzhou University Affiliated Provincial Hospital, Fuzhou 350001, Fujian, China
² Department of Pharmacy, Shengli Clinical Medical College of Fujian Medical University, Fujian Provincial Hospital Fuzhou University Affiliated Provincial Hospital, School of Pharmacy, Fujian Medical University, Fuzhou 350001, Fujian, China

Received:2024-12-24 Revised:2025-02-08 Accepted:2025-02-18 Online:2025-06-02 Published:2025-06-01
Contact: Xiaoxia Wei
Supported by:
The Natural Science Foundation of Fujian, China (Grant No. 2021J01397); Fujian Provincial Health Technology Project (Grant No. 2022GGA010); and Fujian Provincial Joint Funding Project of Scientific and Technological Innovation (Grant No. 2023Y9347).

摘要/Abstract

摘要：

难治性甲状腺癌通常预后较差, 需要更多治疗策略。酪氨酸激酶抑制剂在这些癌症亚型中已显示出相对良好的临床疗效。然而, 现有研究的样本量相对较小, 报告结果存在一定变异。此外, 目前的证据无法直接比较不同酪氨酸激酶抑制剂的相对疗效。本研究旨在通过网络meta分析, 全面评估各种酪氨酸激酶抑制剂治疗难治性甲状腺癌的相对疗效和安全性。通过在PubMed、Cochrane-Library、Embase、Scopus、Web of Science和ClinicalTrials.gov(临床试验注册)等数据库中进行关键词搜索, 我们根据纳入排出标准纳入相关研究。提取相关数据并使用R软件进行贝叶斯网络meta分析。分析结果显示, 在无进展生存期方面, 安罗替尼和阿帕替尼表现出显著优势; 在客观缓解率方面, 卡博替尼和乐伐替尼具有相对优越性; 在疾病控制率方面, 阿帕替尼和乐伐替尼有明显优势; 在任何级别的不良事件方面, 卡博替尼是最安全的选择, 而安罗替尼的安全性最低; 在≥3级不良事件方面, 索拉非尼是最安全的, 而阿帕替尼则有较高风险。研究表明, 安罗替尼, 阿帕替尼, 乐伐替尼和卡博替尼在改善难治性甲状腺癌患者的无进展生存期、客观缓解率和疾病控制率方面表现出优越的疗效; 安罗替尼和阿帕替尼的不良事件发生率较高; 卡博替尼和凡德他尼具有更好的安全性, 但在疗效方面相对较弱。

关键词: 酪氨酸激酶抑制剂, 甲状腺癌, 网络meta分析, 药物疗法

Abstract:

Refractory thyroid cancer is frequently associated with a poor prognosis, necessitating alternative therapeutic approaches. Tyrosine kinase inhibitors (TKIs) have emerged as a promising treatment option, showing generally favorable clinical outcomes in these challenging cancer subtypes. However, the existing body of research is constrained by small sample sizes and variable findings, limiting the ability to directly compare the efficacy of different TKI agents. This study aimed to bridge that gap through a network meta-analysis, evaluating the relative efficacy and safety of various TKIs in managing refractory thyroid cancer. Utilizing systematic keyword searches in databases such as PubMed, Cochrane Library, Embase, Scopus, Web of Science, and ClinicalTrials.gov, we identified studies that met predefined inclusion criteria. Extracted data were analyzed using Bayesian network meta-analysis methods via R software to ensure a comprehensive assessment. Our findings highlighted specific advantages of certain TKIs for various clinical outcomes. In terms of progression-free survival (PFS), Anlotinib and Apatinib showed notable efficacy. For the objective response rate (ORR), Cabozantinib and Lenvatinib demonstrated superior effectiveness, while for disease control rate (DCR), Apatinib and Lenvatinib were advantageous. Regarding safety profiles, Cabozantinib emerged as the safest option for all-grade adverse events (AEs), with Anlotinib showing a higher risk. For severe AEs (grade 3 or higher), Sorafenib proved to be the safest, while Apatinib carried the highest risk. In summary, Anlotinib, Apatinib, Lenvatinib, and Cabozantinib offered significant benefits for PFS, ORR, and DCR in patients with refractory thyroid cancer. However, Anlotinib and Apatinib were associated with higher AE rates, underlining the importance of balancing efficacy with safety. Cabozantinib and Vandetanib, while exhibiting comparatively safer profiles, showed moderate efficacy. These insights underscored the necessity for tailored treatment decisions that carefully weigh the benefits and risks of each TKI agent.

Key words: Tyrosine kinase inhibitors, Thyroid cancer, Network meta-analysis, Drug therapy

Supporting: /attached/file/20250605/20250605231809_445.pdf

朱祎潇, 张丽蓉, 吴文华, 林慧婷, 魏晓霞. 酪氨酸激酶抑制剂在难治性甲状腺癌治疗中的疗效与安全性: 一项网络Meta分析[J]. 中国药学(英文版), 2025, 34(5): 470-484.

Yixiao Zhu, Lirong Zhang, Wenhua Wu, Huiting Lin, Xiaoxia Wei. Efficacy and safety of tyrosine kinase inhibitors in treating refractory thyroid cancer: A network meta-analysis[J]. Journal of Chinese Pharmaceutical Sciences, 2025, 34(5): 470-484.

图/表 9

Figure 1. Flow chart of literature screening.

Table 1. Characteristics of the included literatures.

Figure 2. Risk of bias graph.

Figure 3. Risk of bias summary.

Table 2. Effect model selection of outcome indicator.

Figure 4. Evidence network of PFS (A), ORR (B), DCR (C), ADR (D), ≥ 3ADR (E). The nodes represent the interventions, and the size of the nodes is proportional to the sample size of the respective interventions. The thickness of the connecting lines between nodes indicates the number of studies that compare the two interventions.

Figure 5. Forest plot of network meta-analysis of PFS (A), ORR (B), DCR (C), ADR (D), ≥ 3ADR (E).

Figure 6. The heatmap represents a ranking table of PFS (A), ORR (B), DCR (C), ADR (D), ≥ 3ADR (E). "Treatment" refers to the intervention measures. "Comparator" refers to the control measures. The symbol "**" indicates that at the 95% CI, there is a statistically significant difference between the "Treatment" and its "Comparator".

Figure 7. Probability ranking curve and bar chart of PFS (A), ORR (B), DCR (C), ADR (D). The area under the SUCRA curve is positively correlated with the intervention’s ability to prolong PFS in patients with refractory thyroid cancer.

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酪氨酸激酶抑制剂在难治性甲状腺癌治疗中的疗效与安全性: 一项网络Meta分析

Efficacy and safety of tyrosine kinase inhibitors in treating refractory thyroid cancer: A network meta-analysis

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