第三代EGFR-TKI奥希替尼临床研究进展

邓翔, 杨玉, 李凯, 魏杰, 李怡, 师少军

中国医院药学杂志 ›› 2017, Vol. 37 ›› Issue (24) : 2514-2517.

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中国医院药学杂志 ›› 2017, Vol. 37 ›› Issue (24) : 2514-2517. DOI: 10.13286/j.cnki.chinhosppharmacyj.2017.24.23
综述

第三代EGFR-TKI奥希替尼临床研究进展

  • 邓翔1, 杨玉2, 李凯1, 魏杰1, 李怡1, 师少军2
作者信息 +

Clinical research progress of the third generation EGFR-TKI osimertinib

  • DENG Xiang1, YANG Yu2, LI Kai1, WEI Jie1, LI Yi1, SHI Shao-jun2
Author information +
文章历史 +

摘要

奥希替尼是第三代表皮生长因子受体酪氨酸激酶抑制剂(EGFR-TKI),被批准用于治疗EGFR T790M突变阳性的局部晚期或转移性非小细胞肺癌(NSCLC)的抗肿瘤药物。其疗效显著,耐受性较好,副作用较第一、二代EGFR-TKI更易被接受。对已接受其他EGFR-TKI治疗且出现耐药的患者,奥希替尼可为该类患者带来新的选择。2017年3月22日国家食品药品监督管理总局(CFDA)加速批准了阿斯利康公司的甲磺酸奥希替尼片的进口申请。现就奥希替尼的作用机制、上市情况、临床实验、药动学、耐受性和安全性进行综述,为临床应用提供参考。

Abstract

Osimertinib is a third generation epidermal growth factor receptor tyrosine kinase inhibitor (EGFR-TKI). It is an antineoplastic drug approved for the treatment of EGFR T790M mutation positive for locally advanced or metastatic non small cell lung cancer (NSCLC). It is significantly efficiency, well tolerated, with side effects more likely to be accepted compared with the first and second generation of EGFR-TKI. For persons received other EGFR-TKIs which become resistant, osimertinib would bring a new choice for them. On March 22, 2017, CFDA accelerated the approval of the Astrazeneca application of the imported mesylate osimertinib tablets. In this paper, we review the osimertinib in terms of mechanism of action, market experience, clinical trial, pharmacokinetics, safety and tolerability, to provide a reference for clinical application.

关键词

奥希替尼 / 非小细胞肺癌 / 表皮生长因子受体酪氨酸激酶抑制剂 / 研究进展

Key words

osimertinib / NSCLC / EGFR-TKI / research progress

引用本文

导出引用
邓翔, 杨玉, 李凯, 魏杰, 李怡, 师少军. 第三代EGFR-TKI奥希替尼临床研究进展[J]. 中国医院药学杂志, 2017, 37(24): 2514-2517 https://doi.org/10.13286/j.cnki.chinhosppharmacyj.2017.24.23
DENG Xiang, YANG Yu, LI Kai, WEI Jie, LI Yi, SHI Shao-jun. Clinical research progress of the third generation EGFR-TKI osimertinib[J]. Chinese Journal of Hospital Pharmacy, 2017, 37(24): 2514-2517 https://doi.org/10.13286/j.cnki.chinhosppharmacyj.2017.24.23
中图分类号: R969   

参考文献

[1] Chen W, Zheng R, Baade PD, et al. Cancer statistics in China, 2015[J]. CA-Cancer J Clin, 2016, 66(2):115-132.
[2] 陈万青, 张思维, 邹小农. 中国肺癌发病死亡的估计和流行趋势研究[J]. 中国肺癌杂志, 2010, 13(5):488-493.
[3] Lee DH. Treatments for EGFR-mutant non-small cell lung cancer (NSCLC):The road to a success, paved with failures[J]. Pharmacol Therapeut, 2017,174:1-21.
[4] Gahr S, Stoehr R, Geissinger E, et al. EGFR mutational status in a large series of Caucasian European NSCLC patients:data from daily practice[J]. Br J Cancer, 2013, 109(7):1821-1828.
[5] Seo JS, Ju YS, Lee WC, et al. The transcriptional landscape and mutational profile of lung adenocarcinoma[J]. Genome Res, 2012, 22(11):2109-2119.
[6] Shi Y, Au JS, Thongprasert S, et al. A prospective, molecular epidemiology study of EGFR mutations in Asian patients with advanced non-small-cell lung cancer of adenocarcinoma histology (PIONEER)[J]. J Thorac Oncol, 2014, 9(2):154-162.
[7] Reguart N, Remon J. Common EGFR-mutated subgroups (Del19/L858R)in advanced non-small-cell lung cancer:chasing better outcomes with tyrosine kinase inhibitors[J]. Future Oncol, 2015, 11(8):1245-1257.
[8] Sequist LV, Waltman BA, Dias-Santagata D, et al. Genotypic and histological evolution of lung cancers acquiring resistance to EGFR inhibitors[J]. Sci Transl Med, 2011, 3(75):75ra26.
[9] Yu HA, Arcila ME, Rekhtman N, et al. Analysis of tumor specimens at the time of acquired resistance to EGFR-TKI therapy in 155 patients with EGFR-mutant lung cancers[J]. Clin Cancer Res, 2013, 19(8):2240-2247.
[10] US Food and Drug Administration. TAGRISSOTM (osimertinib) tablet,for oral use Initial U.S.[EB/OL].[2017-04-06]. http://www.accessdata.fda.gov/drugsatfda_docs/label/2015/208065s000lbl.pdf.
[11] 何珩, 黄璐, 许勇. 新型抗非小细胞肺癌药物奥美替尼[J]. 中国新药杂志, 2016(16):1801-1806.
[12] 阿斯利康.甲磺酸奥希替尼片说明书[EB/OL].(2017-03-22)[2017-05-10]. https://www.astrazeneca.com.cn/content/dam/az-cn/pdfs/Tagrisso-Leaflet-IDL-new%20launch.pdf.
[13] AstraZeneca. Tagrisso demonstrates superiority over chemotherapy in EGFR T790M mutation-positive non-small cell lung cancer[EB/OL]. (2016-12-06)[2017-04-06]. https://www.astrazeneca.com/media-centre/press-releases/2016/tagrisso-demonstrates-superiority-over-chemotherapy-in-EGFR-t790m-mutation-positive-non-small-cell-lung-cancer-06122016.html.
[14] Ku BM, Bae YH, Koh J, et al. AZD9291 overcomes T790M-mediated resistance through degradation of EGFR(L858R/T790M)in non-small cell lung cancer cells[J]. Invest New Drugs, 2016, 34(4):407-415.
[15] 张帅, 艾斌. 奥希替尼在晚期非小细胞肺癌的应用[J]. 药品评价, 2016, 13(18):38-41.
[16] Cross DAE, Ashton SE, Ghiorghiu S, et al. AZD9291, an Irreversible EGFR TKI, Overcomes T790M-Mediated Resistance to EGFR Inhibitors in Lung Cancer[J]. Cancer Discov, 2014, 4(9):1046-1061.
[17] Cross DA, Ashton SE, Ghiorghiu S, et al. AZD9291, an irreversible EGFR TKI, overcomes T790M-mediated resistance to EGFR inhibitors in lung cancer[J]. Cancer Discov, 2014, 4(9):1046-1061.
[18] AstraZeneca. TAGRISSO? (osimertinib) approved in EU as first-in-class treatment for patients with EGFR T790M mutation-positive metastatic non-small cell lung cancer[EB/OL]. (2016-02-03)[2017-05-10].https://www.astrazeneca.com/media-centre/press-releases/2016/tagrisso-demonstrates-superiority-over-chemotherapy-in-EGFR-t790m-mutation-positive-non-small-cell-lung-cancer-06122016.html.
[19] AstraZeneca. Tagrisso? (osimertinib) approved in Japan for patients with EGFR T790M mutation-positive metastatic non-small cell lung cancer[EB/OL]. (2016-03-29)[2017-05-10].https://www.astrazeneca.com/media-centre/press-releases/2016/tagrisso-approved-in-japan-for-patients-with-EGFR-t790m-mutation-positive-metastatic-non-small-cell-lung-cancer-29032016.html.
[20] U.S.FOOD & DRUG. Osimertinib (TAGRISSO)[EB/OL]. (2017-03-30)[2017-05-10].https://www.fda.gov/drugs/informationondrugs/approveddrugs/ucm549683.htm.
[21] Jänne PA, Yang JC, Kim DW, et al. AZD9291 in EGFR inhibitor-resistant non-small-cell lung cancer.[J]. New England Journal of Medicine, 2015, 372(18):1689.
[22] 伍筱玫, 丁选胜. 用于非小细胞肺癌治疗的第三代EGFR-TKIs研究进展[J]. 药学进展, 2016,11:826-832.
[23] Ramalingam SS, Yang JC, Lee C, et al. Proceedings of the 16th World Conference on Lung Cancer, Denver, 2015[C]. Denver:International Association for the Study of Lung Cancer Press, 2015.
[24] Mok TS, Wu YL, Ahn MJ, et al. Osimertinib or Platinum-Pemetrexed in EGFR T790M-Positive Lung Cancer[J]. New England Journal of Medicine, 2017, 376(7):629.
[25] US Food and Drug Administration. TAGRISSOTM (osimertinib) tablet,for oral use Initial U.S.[EB/OL].[2015-11-13].http://www.accessdata.fda.gov/Drugsatfda_docs/label/2015/208065s000lbl.pdf.
[26] Planchard D, Brown KH, Kim DW, et al. Osimertinib Western and Asian clinical pharmac-okinetics in patients and healthy volunteers:implications for formulation, dose, and dosing frequency in pivotal clinical studies[J]. Cancer Chemotherapy and Pharmacology, 2016, 77(4):767.
[27] SARAH.GREIG.Osimertinib:first global approval[J].Drugs,2016,76(2):263-273.
[28] AstraZeneca Pharmaceuticals LP. TagrissoTM (osimertinib) tablet, for oral use:US prescribing information. 2015. http://www.fda.gov.Accessed 10 Dec 2015.
[29] Kim D, Yang J, Cross D, et al. Preclinical evidence and clinical cases of AZD9291 activity in EGFR-mutant non-small cell lung cancer (NSCLC) brain metastases (BM)[abstract no. 456P plus poster]. Ann Oncol. 2014;25(Suppl 4):iv152.
[30] Claudia Proto, Martina Imbimbo, Rosaria Gallucci, et al. Epidermal growth factor receptor tyrosine kinase inhibitors for the treatment of central nervous system metastases from non-small cell lung cancer:the present and the future[J]. Transl Lung Cancer Res, 2016, 5(6):563-578.
[31] 于芹, 姜达, 李颖. T790M突变的非小细胞肺癌研究现状与前景[J]. 中国肺癌杂志, 2017, 20(3):199-204.

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