分子靶向药物治疗难治性甲状腺癌的疗效及安全性的meta分析

doi:10.3760/cma.j.issn.1007-1245.2022.17.001

国际医药卫生导报 ›› 2022, Vol. 28 ›› Issue (17): 2369-2376.DOI: 10.3760/cma.j.issn.1007-1245.2022.17.001

• 文献荟萃 • 下一篇

分子靶向药物治疗难治性甲状腺癌的疗效及安全性的meta分析

赵柳燕¹ 宋守君² 薛海波¹

¹滨州医学院附属医院内分泌科，滨州　256603； ²滨州医学院烟台附属医院内分泌科，烟台　264000

收稿日期:2022-06-09 出版日期:2022-09-01 发布日期:2022-10-11
通讯作者: 薛海波，Email：xuehaibo@sina.com
基金资助:
山东省研究生教育创新计划项目（20038612）；

滨州医学院附属医院科研创新团队（202031）；

滨州医学院附属医院后备领军人才（JC2019-03）

Effectiveness and safety of molecular targeted drugs in treatment of refractory thyroid cancer: a meta-analysis

Zhao Liuyan¹, Song Shoujun², Xue Haibo¹

¹Department of Endocrinology, Binzhou Medical University Hospital, Binzhou 256603, China; ²Department of Endocrinology, Yantai Hospital Affiliated to Binzhou Medical University, Yantai 264000, China

Received:2022-06-09 Online:2022-09-01 Published:2022-10-11
Contact: Xue Haibo, Email: xuehaibo@sina.com
Supported by:
Innovation Program of Post-graduate Education of Shandong Province (20038612);

Scientific Research and Innovation Team Project of Binzhou Medical University Hospital (2020301);

Reserved Leading Talent Project of Binzhou Medical University Hospital (JC2019-03)

摘要/Abstract

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

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

赵柳燕宋守君薛海波. 分子靶向药物治疗难治性甲状腺癌的疗效及安全性的meta分析[J]. 国际医药卫生导报, 2022, 28(17): 2369-2376.

Zhao Liuyan, Song Shoujun, Xue Haibo. Effectiveness and safety of molecular targeted drugs in treatment of refractory thyroid cancer: a meta-analysis[J]. International Medicine and Health Guidance News, 2022, 28(17): 2369-2376.

参考文献

[1] La Vecchia C, Malvezzi M, Bosetti C, et al. Thyroid cancer mortality and incidence: a global overview [J]. Int J Cancer, 2015, 136(9): 2187-2195. DOI:10.1002/ijc.29251
[2] Durante C, Haddy N, Baudin E, et al. Long-term outcome of 444 patients with distant metastases from papillary and follicular thyroid carcinoma: benefits and limits of radioiodine therapy[J]. J Clin Endocrinol Metab, 2006, 91(8): 2892-2899. DOI:10.1210/jc.2005-2838
[3] Wells SJ, Asa SL, Dralle H, et al. Revised American Thyroid Association guidelines for the management of medullary thyroid carcinoma[J]. Thyroid, 2015, 25(6): 567-610. DOI:10.1089/thy.2014.0335
[4] Edge SB, Compton CC. The American Joint Committee on Cancer: the 7th edition of the AJCC cancer staging manual and the future of TNM[J]. Ann Surg Oncol, 2010, 17(6): 1471-1474. DOI:10.1245/s10434-010-0985-4
[5] 朱玉娇, 李玥, 宋守君, 等. 表皮生长因子受体表达水平与甲状腺乳头状癌疾病进展的相关性的meta分析[J]. 国际医药卫生导报, 2021, 27(14): 2056-2061. DOI:10.3760/cma.j.issn.1007-1245.2021.14.001.
[6] Santoro M, Moccia M, Federico G, et al. RET gene fusions in malignancies of the thyroid and other tissues[J]. Genes (Basel), 2020, 11(4). DOI:10.3390/genes11040424.
[7] Xing M, Haugen BR, Schlumberger M. Progress in molecular-based management of differentiated thyroid cancer [J]. Lancet, 2013, 381(9871): 1058-1069. DOI: 10.1016/S0140-6736(13)60109-9.
[8] Cumpston M, Li T, Page MJ, et al. Updated guidance for trusted systematic reviews: a new edition of the Cochrane Handbook for Systematic Reviews of Interventions [J]. Cochrane Database Syst Rev, 2019, 10:ED000142. DOI: 10.1002/14651858.ED000142.
[9] Wells SJ, Robinson BG, Gagel RF, et al. Vandetanib in patients with locally advanced or metastatic medullary thyroid cancer: a randomized, double-blind phase Ⅲ trial[J]. J Clin Oncol, 2012, 30(2): 134-141. DOI:10.1200/JCO.2011.35.5040.
[10] Leboulleux S, Bastholt L, Krause T, et al. Vandetanib in locally advanced or metastatic differentiated thyroid cancer: a randomised, double-blind, phase 2 trial[J]. Lancet Oncol, 2012, 13(9): 897-905. DOI:10.1016/S1470-2045(12)70335-2.
[11] Elisei R, Schlumberger MJ, Muller SP, et al. Cabozantinib in progressive medullary thyroid cancer[J]. J Clin Oncol, 2013, 31(29): 3639-3646. DOI: 10.1200/JCO.2012.48. 4659.
[12] Brose MS, Nutting CM, Jarzab B, et al. Sorafenib in radioactive iodine-refractory, locally advanced or metastatic differentiated thyroid cancer: a randomised, double-blind, phase 3 trial [J]. Lancet, 2014, 384(9940): 319-328. DOI:10.1016/S0140-6736(14)60421-9.
[13] Schlumberger M, Tahara M, Wirth LJ, et al. Lenvatinib versus placebo in radioiodine-refractory thyroid cancer [J]. N Engl J Med, 2015, 372(7): 621-630. DOI:10.1056/NEJMoa1406470.
[14] Zheng X, Xu Z, Ji Q, et al. A Randomized, phase Ⅲ study of lenvatinib in Chinese patients with radioiodine-refractory differentiated thyroid cancer[J]. Clinical Cancer Research, 2021, 27(20): 5502-5509. DOI:10.1158/1078-0432.CCR-21-0761.
[15] Li D, Chi Y, Chen X, et al. Anlotinib in locally advanced or metastatic medullary thyroid carcinoma: a randomized, double-blind phase ⅡB trial[J]. Clinical Cancer Research, 2021, 27(13): 3567-3575. DOI:10.1158/1078-0432.CCR-20-2950.
[16] Lin Y, Qin S, Li Z, et al. Apatinib vs placebo in patients with locally advanced or metastatic, radioactive iodine-refractory differentiated thyroid cancer: the REALITY randomized clinical trial[J]. JAMA Oncol, 2022, 8(2): 242-250. DOI:10.1001/jamaoncol.2021.6268.
[17] Knauf JA, Fagin JA. Role of MAPK pathway oncoproteins in thyroid cancer pathogenesis and as drug targets [J]. Curr Opin Cell Biol, 2009, 21(2): 296-303. DOI:10.1016/j.ceb.2009.01.013.
[18] Nozhat Z, Hedayati M. PI3K/AKT pathway and its mediators in thyroid carcinomas[J]. Mol Diagn Ther, 2016, 20(1): 13-26. DOI:10.1007/s40291-015-0175-y.
[19] Alshehri K, Alqurashi Y, Merdad M, et al. Neoadjuvant lenvatinib for inoperable thyroid cancer: a case report and literature review[J]. Cancer Rep (Hoboken), 2022, 5(2): e1466. DOI:10.1002/cnr2.1466.
[20] Huang NS, Wei WJ, Xiang J, et al. The efficacy and safety of anlotinib in neoadjuvant treatment of locally advanced thyroid cancer: a single-arm phase Ⅱ clinical trial[J]. Thyroid, 2021, 31(12): 1808-1813. DOI:10.1089/thy.2021.0307.
[21] Tsoli M, Alexandraki KI, Spei ME, et al. Anti-tumor activity and safety of multikinase inhibitors in advanced and/or metastatic thyroid cancer: a systematic review and network meta-analysis of randomized controlled trials[J]. Horm Metab Res, 2020, 52(1): 25-31. DOI:10.1055/a-1023-4214.
[22] Rendl G, Sipos B, Becherer A, et al. Real-world data for lenvatinib in radioiodine-refractory differentiated thyroid cancer (RELEVANT): a retrospective multicentric analysis of clinical practice in Austria[J]. Int J Endocrinol, 2020: 8834148. DOI:10.1155/2020/8834148.
[23] Sherman EJ, Dunn LA, Ho AL, et al. Phase 2 study evaluating the combination of sorafenib and temsirolimus in the treatment of radioactive iodine-refractory thyroid cancer[J]. Cancer, 2017, 123(21): 4114-4121. DOI:10.1002/cncr.30861.
[24] Subbiah V, Kreitman RJ, Wainberg ZA, et al. Dabrafenib and trametinib treatment in patients with locally advanced or metastatic BRAF V600-mutant anaplastic thyroid cancer[J]. J Clin Oncol, 2018, 36(1): 7-13. DOI:10.1200/JCO.2017.73.6785.
[25] Dierks C, Seufert J, Aumann K, et al. Combination of lenvatinib and pembrolizumab is an effective treatment option for anaplastic and poorly differentiated thyroid carcinoma[J]. Thyroid, 2021, 31(7): 1076-1085. DOI:10.1089/thy.2020.0322.
[26] Oba T, Chino T, Soma A, et al. Comparative efficacy and safety of tyrosine kinase inhibitors for thyroid cancer: a systematic review and meta-analysis [J]. Endocrine Journal, 2020, 67(12): 1215-1226. DOI:10.1507/endocrj.EJ20-0171.
[27] Brose M S, Panaseykin Y, Konda B, et al. A randomized study of lenvatinib 18 mg vs 24 mg in patients with radioiodine-refractory differentiated thyroid cancer[J]. J Clin Endocrinol Metab, 2022, 107(3): 776-787. DOI:10.1210/clinem/dgab731.
[28] de la Fouchardiere C, Godbert Y, Dalban C, et al. Intermittent versus continuous administration of pazopanib in progressive radioiodine refractory thyroid carcinoma: final results of the randomised, multicenter, open-label phase Ⅱ trial PAZOTHYR[J]. Eur J Cancer, 2021, 157: 153-164. DOI:10.1016/j.ejca.2021.07.029.
[29] Brose M S, Bible K C, Chow L, et al. Management of treatment-related toxicities in advanced medullary thyroid cancer [J]. Cancer Treat Rev, 2018, 66: 64-73. DOI:10.1097/CCO.0000000000000534.
[30] Reed N, Glen H, Gerrard G, et al. Expert consensus on the management of adverse events during treatment with lenvatinib for thyroid cancer[J]. Clin Oncol (R Coll Radiol), 2020, 32(5): e145-e153. DOI:10.1016/j.clon.2019.11.010.

分子靶向药物治疗难治性甲状腺癌的疗效及安全性的meta分析

Effectiveness and safety of molecular targeted drugs in treatment of refractory thyroid cancer: a meta-analysis

可视化

摘要/Abstract

引用本文

使用本文

参考文献

相关文章 15

编辑推荐

Metrics

[1]	张文君, 李月明, 何诗琪, 梁淑鸿, 刘映雪, 吴怡玲, 龚业青. 半导体激光联合30%超分子水杨酸治疗痤疮的疗效和护理体会 [J]. 国际医药卫生导报, 2022, 28(7): 1013-1016.
[2]	张力峰, 苏泉心, 高生林, 鹿超, 岳闯, 吴兴宇, 毛卫江, 左立. 改良阴茎成形术治疗青少年男性常见外生殖器畸形的疗效分析[J]. 国际医药卫生导报, 2022, 28(6): 745-748.
[3]	李富云, 薛麦富. 甲泼尼龙和利多卡因治疗难治性突发性聋伴耳鸣的效果[J]. 国际医药卫生导报, 2022, 28(6): 780-783.
[4]	徐丽琴, 洪庆荣, 方圆. 曲普瑞林对特发性中枢性性早熟女童的临床疗效和对骨龄的影响[J]. 国际医药卫生导报, 2022, 28(6): 829-832.
[5]	薛如君, 叶瑞贤, 周欣, 张锡宝. 银屑病光疗的应用及疗效[J]. 国际医药卫生导报, 2022, 28(5): 598-602.
[6]	叶东明, 赖彩永, 伍国豪, 陈智慧, 钟晓健. 尿管管腔内置斑马导丝对导尿困难患者的治疗效果观察[J]. 国际医药卫生导报, 2022, 28(5): 712-714.
[7]	郭智华, 鲁培, 卢晓燕, 黄淑妍, 陈兴. 三七总皂甙对老年不稳定型心绞痛患者Th1/Th2细胞功能失衡的影响[J]. 国际医药卫生导报, 2022, 28(4): 532-536.
[8]	刘慧轩, 何雅军. 血清胸苷激酶1对甲状腺癌诊断价值的meta分析[J]. 国际医药卫生导报, 2022, 28(3): 357-360.
[9]	潘春柳, 黄志华. ICU医用粘胶相关性皮肤损伤患者相关因素的meta分析[J]. 国际医药卫生导报, 2022, 28(2): 270-277.
[10]	周珊汕, 吴智丹. 急性肾功能衰竭患者的综合护理干预分析[J]. 国际医药卫生导报, 2022, 28(2): 278-280.
[11]	于超生于锋邓海燕李军政黄昌锦李慧. 电针法、穴位注射法治疗突发性聋的临床疗效研究[J]. 国际医药卫生导报, 2022, 28(18): 2522-2527.
[12]	白延平郭娅娅. 半量瑞替普酶静脉溶栓对急性心肌梗死患者血流动力、循环内皮细胞及安全性的影响[J]. 国际医药卫生导报, 2022, 28(18): 2600-2603.
[13]	王凤燕侯健张道强宫琪刘传杰韩志浩. 恶性梗阻性黄疸患者PTCD术后发生胆系感染的危险因素[J]. 国际医药卫生导报, 2022, 28(17): 2377-2382.
[14]	刘凤璟　刘辉文　王美玲　陈碧贞. 断指再植患者术后血管危象危险因素的meta分析[J]. 国际医药卫生导报, 2022, 28(15): 2073-2078.
[15]	陈静文　杨志文　方维军. 社区糖尿病合并高血压老年患者的用药情况及疗效评价[J]. 国际医药卫生导报, 2022, 28(15): 2132-2135.