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非小细胞肺癌罕见靶点靶向治疗最新研究进展

李国雨,  何明

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文章导航 > 协和医学杂志  > 2021 >  12(2): 268-274
李国雨, 何明. 非小细胞肺癌罕见靶点靶向治疗最新研究进展[J]. 协和医学杂志, 2021, 12(2): 268-274. doi: 10.3969/j.issn.1674-9081.2020.00.019
引用本文: 李国雨, 何明. 非小细胞肺癌罕见靶点靶向治疗最新研究进展[J]. 协和医学杂志, 2021, 12(2): 268-274. doi: 10.3969/j.issn.1674-9081.2020.00.019
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LI Guo-yu, HE Ming. Research Progress of Targeted Therapy at Rare Targets for Non-small Cell Lung Cancer[J]. Medical Journal of Peking Union Medical College Hospital, 2021, 12(2): 268-274. doi: 10.3969/j.issn.1674-9081.2020.00.019
Citation: LI Guo-yu, HE Ming. Research Progress of Targeted Therapy at Rare Targets for Non-small Cell Lung Cancer[J]. Medical Journal of Peking Union Medical College Hospital, 2021, 12(2): 268-274. doi: 10.3969/j.issn.1674-9081.2020.00.019
shu

非小细胞肺癌罕见靶点靶向治疗最新研究进展

doi: 10.3969/j.issn.1674-9081.2020.00.019
  • 1.

    河北医科大学，石家庄 050000

  • 2.

    河北医科大学第四医院胸外科，石家庄 050000

详细信息
    通讯作者:

    何 明  电话：0311-66696325，E-mail: 2935883213@qq.com

  • 中图分类号: R734.2

Research Progress of Targeted Therapy at Rare Targets for Non-small Cell Lung Cancer

  • 1.

    Hebei Medical University, Shijiazhuang 050000, China

  • 2.

    Department of Thoracic Surgery, the Fourth Hospital of Hebei Medical University, Shijiazhuang 050000, China

More Information

    摘要
  • 摘要: 靶向治疗的快速发展，使非小细胞肺癌(non-small cell lung cancer, NSCLC)的治疗取得革命性突破。相较于放化疗，靶向治疗可显著提高NSCLC患者的5年生存率，改善其预后。靶向治疗针对的靶点除常见的表皮生长因子受体(epidermal growth factor receptor, EGFR)突变基因外，我国肺癌人群中还存在诸多罕见靶点，如间变性淋巴瘤激酶(anaplastic lymphoma kinase, ALK)、间质表皮转化因子(mesenchymal to epithelial transition factor, MET)、人表皮生长因子受体2(human epidermal growth factor receptor 2, HER2)等。近年来，针对这些罕见靶点的新型药物不断更新、相继进入临床使用，并取得了令人惊艳的疗效。本文对以ALK、MET、HER2为靶点的靶向治疗最新研究进展进行梳理和总结，以期为NSCLC的临床治疗提供借鉴。
    Abstract: The rapid development of targeted therapy has made a revolutionary breakthrough in the treatment of non-small cell lung cancer (NSCLC). Compared with radiotherapy and chemotherapy, targeted therapy can significantly increase the five-year survival rate and improve the prognosis of NSCLC patients. In addition to the common epidermal growth factor receptor (EGFR) mutation genes, there are many rare targets for targeted therapy in Chinese lung cancer population, such as anaplastic lymphoma kinase (ALK), mesenchymal to epithelial transition factor (MET), human epidermal growth factor receptor 2 (HER2), etc. In recent years, newly developed medicines for these rare targets have been continuously updated and entered clinical use one after another and have achieved amazing effects. This paper reviews and summarizes the latest research progress of targeted therapy targeting ALK, MET and HER2, in order to provide a reference for the clinical treatment of NSCLC.
    作者贡献：李国雨负责查阅文献、撰写论文；何明负责论文审阅与修改。
    利益冲突：  无
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    • 参考文献(39)
  • [1] 郑荣寿, 孙可欣, 张思维, 等. 2015年中国恶性肿瘤流行情况分析[J]. 中华肿瘤杂志, 2019, 41: 19-28. doi:  10.3760/cma.j.issn.0253-3766.2019.01.005
    [2] 郑轩, 胡毅. 晚期非小细胞肺癌患者抗PD-1治疗前后血清TNF-α水平变化与疗效的关系[J]. 解放军医学院学报, 2019, 40: 231-234. doi:  10.3969/j.issn.2095-5227.2019.03.008
    [3] Genova C, Rossi G, Tagliamento M, et al. Targeted therapy of oncogenic-driven advanced non-small cell lung cancer: recent advances and new perspectives[J]. Expert Rev Respir Med, 2020, 14: 367-383. doi:  10.1080/17476348.2020.1714441
    [4] Atal S, Asokan P, Jhaj R. Recent advances in targeted small-molecule inhibitor therapy for non-small-cell lung cancer-An update[J]. J Clin Pharm Ther, 2020, 45: 580-584. doi:  10.1111/jcpt.13121
    [5] Singh SS, Dahal A, Shrestha L, et al. Genotype Driven Therapy for Non-Small Cell Lung Cancer: Resistance, Pan Inhibitors and Immunotherapy[J]. Curr Med Chem, 2020, 27: 5274-5316. doi:  10.2174/0929867326666190222183219
    [6] Arbour KC, Riely GJ. Systemic Therapy for Locally Adv-anced and Metastatic Non-Small Cell Lung Cancer: A Review[J]. JAMA, 2019, 322: 764-774. doi:  10.1001/jama.2019.11058
    [7] Iwama E, Goto Y, Murakami H, et al. Survival Analysis for Patients with ALK Rearrangement-Positive Non-Small Cell Lung Cancer and a Poor Performance Status Treated with Alectinib: Updated Results of Lung Oncology Group in Kyushu 1401[J]. Oncologist, 2020, 25: 306-e618. doi:  10.1634/theoncologist.2019-0728
    [8] Mok T, Camidge DR, Gadgeel SM, et al. Updated overall survival and final progression-free survival data for patients with treatment-naive advanced ALK-positive non-small-cell lung cancer in the ALEX study[J]. Anna Oncoly, 2020, 31: 1056-1064. doi:  10.1016/j.annonc.2020.04.478
    [9] Hida T, Nokihara H, Kondo M, et al. Alectinib versus crizotinib in patients with ALK-positive non-small-cell lung cancer (J-ALEX): an open-label, randomised phase 3 trial[J]. Lancet, 2017, 390: 29-39. doi:  10.1016/S0140-6736(17)30565-2
    [10] Zhou C, Kim SW, Reungwetwattana T, et al. Alectinib versus crizotinib in untreated Asian patients with anaplastic lymphoma kinase-positive non-small-cell lung cancer (ALESIA): a randomised phase 3 study[J]. Lancet Respir Med, 2019, 7: 437-446. doi:  10.1016/S2213-2600(19)30053-0
    [11] Huang SH, Huang AC, Wang CC, et al. Front-line treatment of ceritinib improves efficacy over crizotinib for Asian patients with anaplastic lymphoma kinase fusion NSCLC: The role of systemic progression control[J]. Thorac Cancer, 2019, 10: 2274-2281. doi:  10.1111/1759-7714.13221
    [12] Nishio M, Felip E, Orlov S, et al. Final Overall Survival and Other Efficacy and Safety Results From ASCEND-3: Phase Ⅱ Study of Ceritinib in ALKi-Naive Patients With ALK-Rearranged NSCLC[J]. J Thorac Oncol, 2020, 15: 609-617. doi:  10.1016/j.jtho.2019.11.006
    [13] Soria JC, Tan DSW, Chiari R, et al. First-line Ceritinib Versus Platinum-Based Chemotherapy in Advanced ALK-rearranged Non-Small-Cell Lung Cancer (ASCEND-4): A Randomised, Open-Label, Phase 3 Study[J]. Lancet, 2017, 389: 917-929. doi:  10.1016/S0140-6736(17)30123-X
    [14] Cho BC, Kim DW, Bearz A, et al. ASCEND-8: A Randomized Phase 1 Study of Ceritinib, 450 mg or 600 mg, Taken With a Low-Fat Meal Versus 750 mg in Fasted State in Patients With Anaplastic Lymphoma Kinase (ALK)-Rearran-ged Metastatic Non-Small Cell Lung Cancer (NSCLC)[J]. J Thorac Oncol, 2017, 12: 1357-1367. doi:  10.1016/j.jtho.2017.07.005
    [15] Cho BC, Obermannova R, Bearz A, et al. Efficacy and Safety of Ceritinib (450 mg/d or 600 mg/d) With Food Versus 750-mg/d Fasted in Patients With ALK Receptor Tyrosine Kinase (ALK)-Positive NSCLC: Primary Efficacy Results From the ASCEND-8 Study[J]. J Thorac Oncol, 2019, 14: 1255-1265. doi:  10.1016/j.jtho.2019.03.002
    [16] Huber RM, Hansen KH, Paz-Ares Rodríguez L, et al. Brigatinib in Crizotinib-Refractory ALK+ NSCLC: 2-Year Follow-up on Systemic and Intracranial Outcomes in the Phase 2 ALTA Trial[J]. J Thorac Oncol, 2020, 15: 404-415. doi:  10.1016/j.jtho.2019.11.004
    [17] Camidge DR, Kim HR, Ahn MJ, et al. Brigatinib Versus Crizotinib in Advanced ALK Inhibitor-Naive ALK-Positive Non-Small Cell Lung Cancer: Second Interim Analysis of the Phase Ⅲ ALTA-1L Trial[J]. J Clin Oncol, 2020, 38: 3592-3603. doi:  10.1200/JCO.20.00505
    [18] Zhu VW, Lin YT, Kim DW, et al. An International Real-World Analysis of the Efficacy and Safety of Lorlatinib Through Early or Expanded Access Programs in Patients With Tyrosine Kinase Inhibitor-Refractory ALK-Positive or ROS1-Positive NSCLC[J]. J Thorac Oncol, 2020, 15: 1484-1496. doi:  10.1016/j.jtho.2020.04.019
    [19] Baldacci S, Besse B, Avrillon V, et al. 1303P Lorlatinib for advanced ALK+ non-small cell lung cancer (NSCLC): Efficacy and safety data from IFCT-1803 LORLATU expanded access program (EAP) cohort[J]. Ann Oncol, 2020, 31: 865-874. doi:  10.1016/j.annonc.2020.08.1663
    [20] Liang H, Wang M. MET Oncogene in Non-Small Cell Lung Cancer: Mechanism of MET Dysregulation and Agents Targeting the HGF/c-Met Axis[J]. Onco Targets Ther, 2020, 13: 2491-2510. doi:  10.2147/OTT.S231257
    [21] Recondo G, Che J, Jänne PA, et al. Targeting MET Dysregulation in Cancer[J]. Cancer Discov, 2020, 10: 922-934. doi:  10.1158/2159-8290.CD-19-1446
    [22] Schuler M, Berardi R, Lim WT, et al. Molecular correlates of response to capmatinib in advanced non-small-cell lung cancer: clinical and biomarker results from a phase Ⅰ trial[J]. Ann Oncol, 2020, 31: 789-797. doi:  10.1016/j.annonc.2020.03.293
    [23] Bang YJ, Su WC, Schuler M, et al. Phase 1 study of capmatinib in MET-positive solid tumor patients: Dose escalation and expansion of selected cohorts[J]. Cancer Sci, 2020, 111: 536-547. doi:  10.1111/cas.14254
    [24] Heist RS, Wolf J, Seto T, et al. OA01.07 Capmatinib (INC280) in METΔEX14-Mutated Advanced NSCLC: Efficacy Data from the Phase 2 Geometry MONO-1 Study[J]. J Thorac Oncol, 2019, 14: S1126-S1138. http://www.sciencedirect.com/science/article/pii/S1556086419333490
    [25] Wolf J, Neal JW, Mansfield AS, et al. 1346P Comparison of clinical outcomes of patients with METΔex14 NSCLC treated with first-line capmatinib in the GEOMETRY mono-1 study with those of a cohort of real-world patients[J]. Ann Oncol, 2020, 31: S863-S874. doi:  10.1016/j.annonc.2020.08.1660
    [26] Goodwin K, Ledezma B, Heist R, etal. MO01.04 Management of Selected Adverse Events With Capmatinib: Institutional Experiences From the GEOMETRY Mono-1 Trial[J]. J Thorac Oncol, 2021, 16: S16-S17. http://www.sciencedirect.com/science/article/pii/S1556086420309187
    [27] Camidge D, Janku F, Bueno A, et al. 1490PDA phase Ⅰa/Ⅱa trial of Sym015, a MET antibody mixture, in patients with advanced solid tumours[J]. Ann Oncol, 2019, 30: 1128-1132. http://www.researchgate.net/publication/336192491_1490PDA_phase_IaIIa_trial_of_Sym015_a_MET_antibody_mixture_in_patients_with_advanced_solid_tumours
    [28] Camidge D, Janku F, Alejandro MB, et al. Safety and preliminary clinical activity of the MET antibody mixture, Sym015 in advanced non-small cell lung cancer (NSCLC) patients with MET amplification/exon 14 deletion (METAmp/Ex14Δ)[J]. J Clin Oncol, 2020, 38: 9510-9519. doi:  10.1200/JCO.2020.38.15_suppl.9510
    [29] Gu Y, Sai Y, Wang J, et al. Preclinical pharmacokinetics, disposition, and translational pharmacokinetic/pharmacodynamic modeling of savolitinib, a novel selective cMet inhibitor[J]. Eur J Pharm Sci, 2019, 136: 104938. doi:  10.1016/j.ejps.2019.05.016
    [30] Sequist LV, Han JY, Ahn MJ, et al. Osimertinib plus savolitinib in patients with EGFR mutation-positive, MET-amplified, non-small-cell lung cancer after progression on EGFR tyrosine kinase inhibitors: interim results from a multicentre, open-label, phase 1b study[J]. Lancet Oncol, 2020, 21: 373-386. doi:  10.1016/S1470-2045(19)30785-5
    [31] Shun L, Jian F, Xingya L, et al. Phase Ⅱ study of savolitinib in patients (pts) with pulmonary sarcomatoid carcinoma (PSC) and other types of non-small cell lung cancer (NSCLC) harboring MET exon 14 skipping mutations (METex14+)[J]. J Clin Oncol, 2020, 38: 9519-9529. doi:  10.1200/JCO.2020.38.15_suppl.9519
    [32] Gan HK, Millward M, Hua Y, et al. First-in-Human Phase Ⅰ Study of the Selective MET Inhibitor, Savolitinib, in Patients with Advanced Solid Tumors: Safety, Pharmacokinetics, and Antitumor Activity[J]. Clin Cancer Res, 2019, 25: 4924-4932. doi:  10.1158/1078-0432.CCR-18-1189
    [33] Wu YL, Cheng Y, Zhou J, et al. Tepotinib plus gefitinib in patients with EGFR-mutant non-small-cell lung cancer with MET overexpression or MET amplification and acquired resistance to previous EGFR inhibitor (INSIGHT study): an open-label, phase 1b/2, multicentre, randomised trial[J]. Lancet Respir Med, 2020, 8: 1132-1143. doi:  10.1016/S2213-2600(20)30154-5
    [34] Paik P, Cortot A, Felip E, et al. A phase Ⅱ trial of tepotinib in patients with non-small cell lung cancer (NSCLC) harboring MET alterations: The VISION study[J]. Ann Oncol, 2019, 30: ii66-ii78. http://www.sciencedirect.com/science/article/pii/S0923753419301310
    [35] Markham A. Tepotinib: First Approval[J]. Drugs, 2020, 80: 829-833. doi:  10.1007/s40265-020-01317-9
    [36] Costa RLB, Czerniecki BJ. Clinical development of immunotherapies for HER2+ breast cancer: a review of HER2-directed monoclonal antibodies and beyond[J]. NPJ Breast Cancer, 2020, 6: 2784-2795. http://www.researchgate.net/publication/339882217_Clinical_development_of_immunotherapies_for_HER2_breast_cancer_a_review_of_HER2-directed_monoclonal_antibodies_and_beyond
    [37] Xu F, Yang G, Xu H, et al. Treatment outcome and clinical characteristics of HER2 mutated advanced non-small cell lung cancer patients in China[J]. Thorac Cancer, 2020, 11: 679-685. doi:  10.1111/1759-7714.13317
    [38] Tsurutani J, Park H, DoiT, et al. OA02.07 Updated Results of Phase 1 Study of DS-8201a in HER2-Expressing or-Mutated Advanced Non-Small-Cell Lung Cancer[J]. J Thorac Oncol, 2018, 13: S324. http://www.sciencedirect.com/science/article/pii/S1556086418312024
    [39] Smit E, Nakagawa K, Nagasaka M, et al. Trastuzumab deruxtecan (T-DXd; DS-8201) in patients with HER2-mutated metastatic non-small cell lung cancer (NSCLC): Interim results of DESTINY-Lung01[J]. J Clin Oncol, 2020, 38: 9504. doi:  10.1200/JCO.2020.38.15_suppl.9504
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出版历程
  • 收稿日期:  2020-07-22
  • 录用日期:  2020-10-14
  • 网络出版日期:  2020-12-16
  • 刊出日期:  2021-05-30

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