Abstract: Objective　To systematically evaluate the effectiveness and safety of molecular targeted drugs in the treatment of refractory thyroid cancer by meta-analysis, and to provide valuable evidence-based medical information for clinical application. Methods　The PubMed, Embase, the Cochrane Library, Web of Science, CNKI, Wanfang Data, and SinoMed databases were searched for targeted therapy literatures of thyroid cancer from their establishment to April 13, 2022. The studies were screened, the basic data were extracted, and the risk of bias in the included studies was evaluated. The RevMan 5.4 software was used to perform meta-analysis. Results　Eight studies were included. The total sample size of the experimental group, treated with molecular targeted drugs, was 1 201, and that of the control group, treated with placebos, was 748. Meta-analysis showed that, compared with placebos, molecular targeted drugs had a better objective response rate (ORR) (RR=14.19, 95%CI 4.12-48.93, P<0.000 1) and a disease control rate (DCR) (RR=1.40, 95%CI 1.20-1.63, P<0.000 1), and significantly improved the progression-free survival (PFS) of the refractory thyroid cancer patients (HR=0.35, 95%CI 0.25-0.51, P<0.000 01). The incidence of ≥grade 3 adverse events (AEs) in the experimental group was higher than that in the control group (RR=3.85, 95%CI 2.90-7.10, P<0.000 1). The most common AEs (≥grade 3) were diarrhea, hypertension, fatigue, palmar-plantar erythrodsesthesia syndrome, decreased appetite, and decreased weight. Conclusions　Molecular targeted drugs have better clinical curative effects, and most AEs can be controlled by adjusting the dose and giving supportive treatment. Therefore, molecular targeted drugs can become a new option for refractory thyroid cancer.

Key words: Molecular targeted drugs, Refractory thyroid cancer, Curative effect, Safety, Meta-analysis

摘要： 目的　对分子靶向药物治疗难治性甲状腺癌的疗效及安全性进行meta分析，为临床应用提供有价值的循证医学证据。方法　检索PubMed、Embase、the Cochrane Library、Web of Science、中国知网、万方数据知识服务平台以及中国生物医学文献服务系统从建库到2022年4月13日关于甲状腺癌分子靶向治疗的文献，筛选文献提取数据，评价纳入研究的偏倚风险，采用RevMan5.4软件进行meta分析。结果　共纳入8项研究，试验组（分子靶向药物）样本量为1 201例，对照组（安慰剂）样本量为748例。meta分析结果显示，相比于安慰剂，分子靶向药物有更佳的客观缓解率（objective response rate，ORR）（RR=14.19，95%CI 4.12～48.93，P<0.000 1）以及疾病控制率（disease control rate，DCR）（RR=1.40，95%CI 1.20～1.63，P<0.000 1），并且明显提高了难治性甲状腺癌患者的无进展生存期（progression-free survival，PFS）（HR=0.35，95%CI 0.25～0.51，P<0.000 01）。试验组≥3级不良事件（adverse events，AEs）发生率高于对照组（RR=3.85，95%CI 2.90～7.10，P<0.000 1），主要为腹泻、高血压、疲劳、手足综合征、食欲下降以及体质量下降。结论　分子靶向药物具有良好的疗效，并且通过调整剂量和给予支持治疗可使大部分AEs得以控制。因此，分子靶向药物可成为治疗难治性甲状腺癌新的选择。                    

关键词: 分子靶向药物, 难治性甲状腺癌, 疗效, 安全性, meta分析