|
|
HER2阳性非小细胞肺癌临床治疗效果及安全性研究进展
|
Abstract:
目的：肺癌作为一种常见的恶性肿瘤，是肿瘤患者死亡的主要原因之一。近年来，许多研究报道了靶向及免疫治疗在HER2阳性非小细胞肺癌(NSCLC)中的疗效。然而，目前仍然没有确切的方法应用于临床治疗中。方法：通过系统检索多个数据库，包括知网、万方、PubMed、Web of Science、Cochrane Library、Embase以及一些主要的肿瘤学会议，收集与HER2阳性NSCLC相关的临床试验，以了解各种治疗在HER2阳性NSCLC中的疗效。结果：系统分析发现在抗体药物偶联物(antibody-drug conju-gates, ADCs)、单克隆抗体、酪氨酸激酶抑制剂(tyrosine kinase inhibitors, TKIs)、免疫检查点抑制剂(immune checkpoint inhibitors, ICIs)等药物中，选择性TKIs及ADCs显示出了良好的抗肿瘤活性；单克隆抗体联合化疗取得了较好的结果；免疫治疗或免疫联合化疗作为一线治疗HER2阳性NSCLC也是一种有前景的干预措施。结论：选择性TKIs及ADCs是目前很有前景的HER2阳性NSCLC治疗药物，且具有可接受的安全性。
Objective: Lung cancer, as a common malignant tumor, is one of the major causes of death in tumor patients. In recent years, many studies have reported the efficacy of targeted and immunotherapy in HER2-positive non-small cell lung cancer (NSCLC). However, there is still no definitive method ap-plied in clinical treatment. Methods: We collected clinical trials related to HER2-positive NSCLC by systematically searching multiple databases, including CNKI, Wanfang, PubMed, Web of Science, Cochrane Library, Embase, and some major oncology conferences, to understand the efficacy of var-ious treatments in HER2-positive NSCLC. Results: Systematic analysis revealed that among anti-body-drug conjugates (ADCs), monoclonal antibodies, tyrosine kinase inhibitors (TKIs), and im-mune checkpoint inhibitors (ICIs), selective TKIs and ADCs showed good antitumor activity; mono-clonal antibodies in combination with chemotherapy yielded better results; and immunotherapy or immune-conjugated chemotherapy as a first-line treatment for HER2-positive NSCLC is also a prom-ising intervention. Conclusions: Selective TKIs and ADCs are currently promising agents for the treatment of HER2-positive NSCLC with an acceptable safety profile.
| [1] | Sung, H., Ferlay, J., Siegel, R.L., et al. (2021) Global Cancer Statistics 2020: GLOBOCAN Estimates of Incidence and Mortality Worldwide for 36 Cancers in 185 Countries. CA: A Cancer Journal for Clinicians, 71, 209-249.
https://doi.org/10.3322/caac.21660 |
| [2] | Siegel, R.L., Miller, K.D., Fuchs, H.E., et al. (2021) Cancer Statistics, 2021. CA: A Cancer Journal for Clinicians, 71, 7-33. https://doi.org/10.3322/caac.21654 |
| [3] | Chi, F., Wu, R., Jin, X., et al. (2016) HER2 Induces Cell Proliferation and Invasion of Non-Small-Cell Lung Cancer by Upregulating COX-2 Expression via MEK/ERK Signaling Pathway. OncoTargets and Therapy, 9, 2709-2716.
https://doi.org/10.2147/OTT.S96197 |
| [4] | Riudavets, M., Sullivan, I., Abdayem, P., et al. (2021) Targeting HER2 in Non-Small-Cell Lung Cancer (NSCLC): A Glimpse of Hope? An Updated Review on Therapeutic Strategies in NSCLC Harbouring HER2 Alterations. ESMO Open, 6, Article ID: 100260. https://doi.org/10.1016/j.esmoop.2021.100260 |
| [5] | Aix, S.P., Navarro, A., Bernabe, R., et al. (2021) 464 2SMALL (Nct04253145) Phase I Part: Lurbinectidine (Lur) in Combination with Atezolizumab (Atz) for Second Line Extensive Stage Small Cell Lung Cancer (Es-Sclc) Patients (Pts). Journal for Immunotherapy of Cancer, 9, A493. https://doi.org/10.1136/jitc-2021-SITC2021.464 |
| [6] | Barlesi, F., Mazieres, J., Merlio, J.P., et al. (2016) Routine Molecular Profiling of Patients with Advanced Non-Small-Cell Lung Cancer: Results of a 1-Year Nationwide Pro-gramme of the French Cooperative Thoracic Intergroup (IFCT). The Lancet, 387, 1415-1426. https://doi.org/10.1016/S0140-6736(16)00004-0 |
| [7] | Yang, G., Yang, Y., Liu, R., et al. (2022) First-Line Immu-notherapy or Angiogenesis Inhibitor plus Chemotherapy for HER2-Altered NSCLC: A Retrospective Real-World POLISH Study. Therapeutic Advances in Medical Oncology, 14.
https://doi.org/10.1177/17588359221082339 |
| [8] | Zhou, J., Hu, J., Song, Y., et al. (2020) Clinical Outcomes of Patients with HER2-Mutant Advanced Lung Cancer: Chemotherapies versus HER2-Directed Therapies. American Jour-nal of Respiratory and Critical Care Medicine, 201, A2455. https://doi.org/10.1164/ajrccm-conference.2020.201.1_MeetingAbstracts.A2455 |
| [9] | Wang, Y., Zhang, S.J., Wu, F.Y., et al. (2018) Outcomes of Pemetrexed-Based Chemotherapies In-Mutant Lung Cancers. BMC Cancer, 18, Article No. 326. https://doi.org/10.1186/s12885-018-4277-x |
| [10] | Lewis Phillips, G.D., Li, G., Dugger, D.L., et al. (2008) Targeting HER2-Positive Breast Cancer with Trastuzumab-DM1: An Antibody-Cytotoxic Drug Conjugate. Cancer Re-search, 68, 9280-9290.
https://doi.org/10.1158/0008-5472.CAN-08-1776 |
| [11] | De Langen, A.J., Jebbink, M., Hashemi, S.M.S., et al. (2018) Trastuzumab and Paclitaxel in Patients with EGFR Mutated NSCLC That Express HER2 after Progression on EGFR TKI Treatment. British Journal of Cancer, 119, 558-564. https://doi.org/10.1038/s41416-018-0194-7 |
| [12] | Li, B.T., Shen, R., Buonocore, D., et al. (2018) Ado-Trastuzumab Emtansine for Patients with HER2-Mutant Lung Cancers: Results from a Phase II Basket Trial. Journal of Clinical On-cology: Official Journal of the American Society of Clinical Oncology, 36, 2532-2537. https://doi.org/10.1200/JCO.2018.77.9777 |
| [13] | Iwama, E., Zenke, Y., Sugawara, S., et al. (2022) Trastuzumab Emtansine for Patients with Non-Small Cell Lung Cancer Positive for Human Epidermal Growth Factor2 Exon-20 Inser-tion Mutations. European Journal of Cancer, 162, 99-106. https://doi.org/10.1016/j.ejca.2021.11.021 |
| [14] | Hotta, K., Aoe, K., Kozuki, T., et al. (2018) A Phase II Study of Trastuzumab Emtansine in HER2-Positive Non-Small Cell Lung Cancer. Journal of Thoracic Oncology, 13, 273-279. https://doi.org/10.1016/j.jtho.2017.10.032 |
| [15] | Peters, S., Stahel, R., Bubendorf, L., et al. (2019) Trastuzumab Emtansine (T-DM1) in Patients with Previously Treated HER2-Overexpressing Metastatic Non-Small Cell Lung Cancer: Efficacy, Safety, and Biomarkers. Clinical Cancer Re-search, 25, 64-72. https://doi.org/10.1158/1078-0432.CCR-18-1590 |
| [16] | Ogitani, Y., Aida, T., Hagihara, K., et al. (2016) DS-8201a, a Novel HER2-Targeting ADC with a Novel DNA Topoisomerase I Inhibitor, Demonstrates a Prom-ising Antitumor Efficacy with Differentiation from T-DM1. Clinical Cancer Research, 22, 5097-5108. https://doi.org/10.1158/1078-0432.CCR-15-2822 |
| [17] | Ogitani, Y., Hagihara, K., Oitate, M., et al. (2016) Bystand-er Killing Effect of DS-8201a, a Novel Anti-Human Epidermal Growth Factor Receptor 2 Antibody-Drug Conjugate, in Tumors with Human Epidermal Growth Factor Receptor 2 Heterogeneity. Cancer Science, 107, 1039-1046. https://doi.org/10.1111/cas.12966 |
| [18] | Tsurutani, J., Iwata, H., Krop, I., et al. (2020) Targeting HER2 with Trastuzumab Deruxtecan: A Dose-Expansion, Phase I Study in Multiple Advanced Solid Tumors. Cancer Discovery, 10, 688-701.
https://doi.org/10.1158/2159-8290.CD-19-1014 |
| [19] | Li, B.T., Smit, E.F., Goto, Y., et al. (2022) Trastuzumab Deruxtecan in HER2-Mutant Non-Small-Cell Lung Cancer. The New England Journal of Medicine, 386, 241-251. https://doi.org/10.1056/NEJMoa2112431 |
| [20] | Goto, K., Goto, Y., Kubo, T., et al. (2023) Trastuzumab Deruxtecan in Patients with HER2-Mutant Metastatic Non-Small-Cell Lung Cancer: Primary Results from the Randomized, Phase II DESTINY-Lung02 Trial. Journal of Clinical Oncology: Official Journal of the American Society of Clinical Oncology, 41, 4852-4863. |
| [21] | Klapper, L.N., Waterman, H., Sela, M., et al. (2000) Tumor-Inhibitory Antibodies To HER-2/ErbB-2 May Act by Recruiting C-Cbl and Enhancing Ubiquitination of HER-2. Cancer Research, 60, 3384-3388. |
| [22] | Zinner, R.G., Glisson, B.S., Fossella, F.V., et al. (2004) Trastuzumab in Combination with Cisplatin and Gemcitabine in Patients with Her2-Overexpressing, Untreated, Advanced Non-Small Cell Lung Cancer: Report of A Phase II Trial and Findings Regarding Optimal Identification of Patients with Her2-Overexpressing Disease. Lung Can-cer, 44, 99-110. https://doi.org/10.1016/j.lungcan.2003.09.026 |
| [23] | Gatzemeier, U., Groth, G., Butts, C., et al. (2004) Randomized Phase II Trial of Gemcitabine-Cisplatin with or without Trastuzumab in HER2-Positive Non-Small-Cell Lung Cancer. Annals of Oncology, 15, 19-27.
https://doi.org/10.1093/annonc/mdh031 |
| [24] | Lara, P.N., Laptalo, L., Longmate, J., et al. (2004) Trastuzumab plus Docetaxel in HER2/Neu-Positive Non-Small-Cell Lung Cancer: A California Cancer Consortium Screening and Phase II Trial. Clinical Lung Cancer, 5, 231-236.
https://doi.org/10.3816/CLC.2004.n.004 |
| [25] | Langer, C.J., Stephenson, P., Thor, A., et al. (2004) Trastuzumab in the Treatment of Advanced Non-Small-Cell Lung Cancer: Is There a Role? Focus on Eastern Cooperative Oncology Group Study 2598. Journal of Clinical Oncology: Official Journal of the American Society of Clinical Oncology, 22, 1180-1187.
https://doi.org/10.1200/JCO.2004.04.105 |
| [26] | Mazières, J., Barlesi, F., Filleron, T., et al. (2016) Lung Cancer Pa-tients with HER2 Mutations Treated with Chemotherapy and HER2-Targeted Drugs: Results from the European EUHER2 Cohort. Annals of Oncology, 27, 281-286.
https://doi.org/10.1093/annonc/mdv573 |
| [27] | Hainsworth, J.D., Meric-Bernstam, F., Swanton, C., et al. (2018) Targeted Therapy for Advanced Solid Tumors on the Basis of Molecular Profiles: Results from MyPathway, an Open-Label, Phase IIa Multiple Basket Study. Journal of Clinical Oncology: Official Journal of the American Society of Clinical Oncology, 36, 536-542.
https://doi.org/10.1200/JCO.2017.75.3780 |
| [28] | Mazieres, J., Lafitte, C., Ricordel, C., et al. (2022) Combination of Trastuzumab, Pertuzumab, and Docetaxel in Patients with Advanced Non-Small-Cell Lung Cancer Harboring HER2 Mutations: Results from the IFCT-1703 R2D2 Trial. Journal of Clinical Oncology: Official Journal of the American So-ciety of Clinical Oncology, 40, 719-728.
https://doi.org/10.1200/JCO.21.01455 |
| [29] | Wang, Y., Jiang, T., Qin, Z., et al. (2019) HER2 Exon 20 Insertions in Non-Small-Cell Lung Cancer Are Sensitive to the Irreversible Pan-HER Receptor Tyrosine Kinase Inhibitor Pyrotinib. Annals of Oncology, 30, 447-455.
https://doi.org/10.1093/annonc/mdy542 |
| [30] | Zhou, C., Li, X., Wang, Q., et al. (2020) Pyrotinib in HER2-Mutant Advanced Lung Adenocarcinoma after Platinum-Based Chemotherapy: A Multicenter, Open-Label, Single-Arm, Phase II Study. Journal of Clinical Oncology: Official Journal of the American Society of Clinical Oncology, 38, 2753-2761. https://doi.org/10.1200/JCO.20.00297 |
| [31] | Song, Z.B., Lv, D.Q., Chen, S.Q., et al. (2022) Pyrotinib in Patients with HER2-Amplified Advanced Non-Small Cell Lung Cancer: A Prospective, Multicenter, Single-Arm Trial. Clinical Cancer Research, 28, 461-467.
https://doi.org/10.1158/1078-0432.CCR-21-2936 |
| [32] | Song, Z., Li, Y., Chen, S., et al. (2022) Efficacy and Safety of Pyrotinib in Advanced Lung Adenocarcinoma with HER2 Mutations: A Multicenter, Single-Arm, Phase II Trial. BMC Medicine, 20, Article No. 42.
https://doi.org/10.1186/s12916-022-02245-z |
| [33] | Liu, S.M., Tu, H.Y., Wei, X.W., et al. (2023) First-Line Pyro-tinib in Advanced HER2-Mutant Non-Small-Cell Lung Cancer: A Patient-Centric Phase 2 Trial. Nature Medicine, 29, 2079-2086. https://doi.org/10.1038/s41591-023-02461-x |
| [34] | Yang, G., Xu, H., Yang, Y., et al. (2022) Pyrotinib Combined with Apatinib for Targeting Metastatic Non-Small Cell Lung Cancer with HER2 Alterations: A Prospective, Open-Label, Single-Arm Phase 2 Study (PATHER2). BMC Medicine, 20, Article No. 277. https://doi.org/10.1186/s12916-022-02470-6 |
| [35] | Ai, X., Song, Z., Jian, H., et al. (2021) Pyrotinib Combined with Thalidomide in Advanced Non-Small-Cell Lung Cancer Patients Harboring HER2 Exon 20 Insertions (PRIDE): Protocol of an Open-Label, Single-Arm Phase II Trial. BMC Cancer, 21, Article No. 1033. https://doi.org/10.1186/s12885-021-08759-8 |
| [36] | Robichaux, J.P., Elamin, Y.Y., Tan, Z., et al. (2018) Mecha-nisms and Clinical Activity of an EGFR and HER2 Exon 20-Selective Kinase Inhibitor in Non-Small Cell Lung Cancer. Nature Medicine, 24, 638-646.
https://doi.org/10.1038/s41591-018-0007-9 |
| [37] | Koga, T., Kobayashi, Y., Tomizawa, K., et al. (2018) Activity of a Novel HER2 Inhibitor, Poziotinib, for HER2 Exon 20 Mutations in Lung Cancer and Mechanism of Acquired Re-sistance: An in Vitro Study. Lung Cancer, 126, 72-79.
https://doi.org/10.1016/j.lungcan.2018.10.019 |
| [38] | Robichaux, J.P., Elamin, Y.Y., Vijayan, R.S.K., et al. (2019) Pan-Cancer Landscape and Analysis of ERBB2 Mutations Identifies Poziotinib as a Clinically Active Inhibitor and En-hancer of T-DM1 Activity. Cancer Cell, 36, 444-457.e447. https://doi.org/10.1016/j.ccell.2019.09.001 |
| [39] | Le, X., Cornelissen, R., Garassino, M., et al. (2022) Poziotinib in Non-Small-Cell Lung Cancer Harboring HER2 Exon 20 In-sertion Mutations after Prior Therapies: ZENITH20-2 Trial. Journal of Clinical Oncology: Official Journal of the Ameri-can Society of Clinical Oncology, 40, 710-718. https://doi.org/10.1200/JCO.21.01323 |
| [40] | Cornelissen, R., Prelaj, A., Sun, S., et al. (2023) Poziotinib in Treatment-Naive NSCLC Harboring HER2 Exon 20 Mutations: ZENITH20-4, a Multicenter, Multicohort, Open-Label, Phase 2 Trial (Cohort 4). Journal of Thoracic Oncology, 18, 1031-1041. https://doi.org/10.1016/j.jtho.2023.03.016 |
| [41] | Elamin, Y.Y., Robichaux, J.P., Carter, B.W., et al. (2022) Pozio-tinib for Patients with HER2 Exon 20 Mutant Non-Small-Cell Lung Cancer: Results from a Phase II Trial. Journal of Clinical Oncology: Official Journal of the American Society of Clinical Oncology, 40, 702-709. https://doi.org/10.1200/JCO.21.01113 |
| [42] | De Grève, J., Moran, T., Graas, M.P., et al. (2015) Phase II Study of Afatinib, an Irreversible ErbB Family Blocker, in Demographically and Genotypically Defined Lung Adenocarcinoma. Lung Cancer, 88, 63-69.
https://doi.org/10.1016/j.lungcan.2015.01.013 |
| [43] | Peters, S., Curioni-Fontecedro, A., Nechushtan, H., et al. (2018) Activity of Afatinib in Heavily Pretreated Patients with ERBB2 Mutation-Positive Advanced NSCLC: Findings from a Global Named Patient Use Program. Journal of Thoracic Oncology, 13, 1897-1905. https://doi.org/10.1016/j.jtho.2018.07.093 |
| [44] | Dziadziuszko, R., Smit, E.F., Dafni, U., et al. (2019) Afatinib in NSCLC with HER2 Mutations: Results of the Prospective, Open-Label Phase II NICHE Trial of European Thoracic Oncology Platform (ETOP). Journal of Thoracic Oncology, 14, 1086-1094. https://doi.org/10.1016/j.jtho.2019.02.017 |
| [45] | Fan, Y., Chen, J., Zhou, C., et al. (2020) Afatinib in Patients with Advanced Non-Small Cell Lung Cancer Harboring HER2 Mutations, Previously Treated with Chemotherapy: A Phase II Trial. Lung Cancer, 147, 209-213.
https://doi.org/10.1016/j.lungcan.2020.07.017 |
| [46] | Kris, M.G., Camidge, D.R., Giaccone, G., et al. (2015) Target-ing HER2 Aberrations as Actionable Drivers in Lung Cancers: Phase II Trial of the Pan-HER Tyrosine Kinase Inhibitor Dacomitinib in Patients with HER2-Mutant or Amplified Tumors. Annals of Oncology, 26, 1421-1427. https://doi.org/10.1093/annonc/mdv186 |
| [47] | Nagano, M., Kohsaka, S., Ueno, T., et al. (2018) High-Throughput Functional Evaluation of Variants of Unknown Significance in ERBB2. Clinical Cancer Research, 24, 5112-5122. https://doi.org/10.1158/1078-0432.CCR-18-0991 |
| [48] | Hyman, D.M., Piha-Paul, S.A., Won, H., et al. (2018) HER Kinase Inhibition in Patients with HER2- and HER3-Mutant Cancers. Nature, 554, 189-194. https://doi.org/10.1038/nature25475 |
| [49] | Sharma, P. and Allison, J.P. (2015) The Future of Immune Checkpoint Therapy. Science, 348, 56-61.
https://doi.org/10.1126/science.aaa8172 |
| [50] | Pardoll, D.M. (2012) The Blockade of Immune Checkpoints in Cancer Immunotherapy. Nature Reviews Cancer, 12, 252-264. https://doi.org/10.1038/nrc3239 |
| [51] | Catania, C., Passaro, A., Rocco, E.G., et al. (2016) Dramatic Antitumor Activity of Nivolumab in Advanced HER2-Positive Lung Cancer. Clinical Lung Cancer, 17, E179-E183. https://doi.org/10.1016/j.cllc.2016.05.004 |
| [52] | Chuang, J.C., Stehr, H., Liang, Y., et al. (2017) ERBB2-Mutated Metastatic Non-Small Cell Lung Cancer: Response and Resistance to Targeted Therapies. Journal of Thoracic Oncology, 12, 833-842.
https://doi.org/10.1016/j.jtho.2017.01.023 |
| [53] | Mazieres, J., Drilon, A., Lusque, A., et al. (2019) Immune Check-point Inhibitors for Patients with Advanced Lung Cancer and Oncogenic Driver Alterations: Results from the IMMUNOTARGET Registry. Annals of Oncology, 30, 1321-1328. https://doi.org/10.1093/annonc/mdz167 |
| [54] | Guisier, F., Dubos-Arvis, C., Vinas, F., et al. (2020) Efficacy and Safety of Anti-PD-1 Immunotherapy in Patients with Advanced NSCLC with BRAF, HER2, or MET Mutations or RET Translocation: GFPC 01-2018. Journal of Thoracic Oncology, 15, 628-636. https://doi.org/10.1016/j.jtho.2019.12.129 |
| [55] | Saalfeld, F.C., Wenzel, C., Christopoulos, P., et al. (2021) Efficacy of Immune Checkpoint Inhibitors Alone or in Combination with Chemotherapy in NSCLC Harboring ERBB2 Mutations. Journal of Thoracic Oncology, 16, 1952-1958. https://doi.org/10.1016/j.jtho.2021.06.025 |
| [56] | Chu, X., Qiang, H., Xie, M., et al. (2022) Treatment Efficacy of HER2-Mutant Lung Adenocarcinoma by Immune Checkpoint Inhibitors: A Multicenter Retrospective Study. Cancer Immunology Immunotherapy, 71, 1625-1631.
https://doi.org/10.1007/s00262-021-03100-5 |
| [57] | Zhao, S., Xian, X., Tian, P., et al. (2021) Efficacy of Combina-tion Chemo-Immunotherapy as a First-Line Treatment for Advanced Non-Small-Cell Lung Cancer Patients with HER2 Alterations: A Case Series. Frontiers in Oncology, 11, Article ID: 633522. https://doi.org/10.3389/fonc.2021.633522 |
