抗体偶联药物在非小细胞肺癌中的应用

doi:10.3760/cma.j.cn371439-20220309-00055

摘要/Abstract

摘要：

抗体偶联药物（ADC）以其抗体靶向性的独特优势,克服了传统化疗和靶向治疗的局限性,并在肺癌治疗领域取得了突破性的成绩。目前ADC在非小细胞肺癌中的研究主要涉及靶点有HER2、HER3、TROP2、MET、CEACAM5,多种药物已通过严格的临床试验,并表现出良好的安全性和有效性,为肺癌个性化治疗提供了理论依据。

关键词: 抗体, 细胞毒素类, 肺肿瘤, 分子靶向治疗

Abstract:

Antibody-drug conjugates （ADCs） have overcome the limitations of traditional chemotherapy and targeted therapy with unique advantage of antibody targeting, and made breakthrough achievements in the treatment of lung cancer. At present, the researches of ADCs in non-small cell lung cancer mainly involve HER2, HER3, TROP2, MET, CEACAM5. Many ADCs have passed rigorous clinical trials, and have shown good safety and efficacy, which provides theoretical basis for individualized treatment of lung cancer.

Key words: Antibodies, Cytotoxins, Lung neoplasms, Molecular targeted therapy

张静娴, 易丹, 李小江. 抗体偶联药物在非小细胞肺癌中的应用[J]. 国际肿瘤学杂志, 2022, 49(5): 296-301.

Zhang Jingxian, Yi Dan, Li Xiaojiang. Application of antibody-drug conjugates in the treatment of non-small cell lung cancer[J]. Journal of International Oncology, 2022, 49(5): 296-301.

参考文献 33

[1]	Sung H, Ferlay J, Siegel RL, et al. Global cancer statistics 2020: GLOBOCAN estimates of incidence and mortality worldwide for 36 cancers in 185 countries[J]. CA Cancer J Clin, 2021, 71(3): 209-249. DOI: 10.3322/caac.21660. doi: 10.3322/caac.21660
[2]	Lim ZF, Ma PC. Emerging insights of tumor heterogeneity and drug resistance mechanisms in lung cancer targeted therapy[J]. J Hematol Oncol, 2019, 12(1): 134. DOI: 10.1186/s13045-019-0818-2. doi: 10.1186/s13045-019-0818-2
[3]	Wolska-Washer A, Robak T. Safety and tolerability of antibody-drug conjugates in cancer[J]. Drug Saf, 2019, 42(2): 295-314. DOI: 10.1007/s40264-018-0775-7. doi: 10.1007/s40264-018-0775-7
[4]	Riudavets M, Sullivan I, Abdayem P, et al. Targeting HER2 in non-small-cell lung cancer (NSCLC): a glimpse of hope? An updated review on therapeutic strategies in NSCLC harbouring HER2 alterations[J]. ESMO Open, 2021, 6(5): 100260. DOI: 10.1016/j.esmoop.2021.100260. doi: 10.1016/j.esmoop.2021.100260
[5]	Arcila ME, Chaft JE, Nafa K, et al. Prevalence, clinicopathologic associations, and molecular spectrum of ERBB2 (HER2) tyrosine kinase mutations in lung adenocarcinomas[J]. Clin Cancer Res, 2012, 18(18): 4910-4918. DOI: 10.1158/1078-0432.CCR-12-0912. doi: 10.1158/1078-0432.CCR-12-0912 pmid: 22761469
[6]	Burris HA 3rd, Rugo HS, Vukelja SJ, et al. Phase Ⅱ study of the antibody drug conjugate trastuzumab-DM1 for the treatment of human epidermal growth factor receptor 2 (HER2)-positive breast cancer after prior HER2-directed therapy[J]. J Clin Oncol, 2011, 29(4): 398-405. DOI: 10.1200/JCO.2010.29.5865. doi: 10.1200/JCO.2010.29.5865
[7]	Montemurro F, Ellis P, Anton A, et al. Safety of trastuzumab emtansine (T-DM1) in patients with HER2-positive advanced breast cancer: primary results from the KAMILLA study cohort 1[J]. Eur J Cancer, 2019, 109: 92-102. DOI: 10.1016/j.ejca.2018.12.022. doi: S0959-8049(18)31577-6 pmid: 30708264
[8]	Cretella D, Saccani F, Quaini F, et al. Trastuzumab emtansine is active on HER-2 overexpressing NSCLC cell lines and overcomes gefitinib resistance[J]. Mol Cancer, 2014, 13: 143. DOI: 10.1186/1476-4598-13-143. doi: 10.1186/1476-4598-13-143 pmid: 24898067
[9]	Peters S, Stahel R, Bubendorf L, et al. Trastuzumab emtansine (T-DM1) in patients with previously treated HER2-overexpressing metastatic non-small cell lung cancer: efficacy, safety, and biomarkers[J]. Clin Cancer Res, 2019, 25(1): 64-72. DOI: 10.1158/1078-0432.CCR-18-1590. doi: 10.1158/1078-0432.CCR-18-1590
[10]	Li BT, Shen R, Buonocore D, et al. Ado-trastuzumab emtansine for patients with HER2-mutant lung cancers: results from a phase Ⅱ basket trial[J]. J Clin Oncol, 2018, 36(24): 2532-2537. DOI: 10.1200/JCO.2018.77.9777. doi: 10.1200/JCO.2018.77.9777
[11]	Xu Z, Guo D, Jiang Z, et al. Novel HER2-targeting antibody-drug conjugates of trastuzumab beyond T-DM1 in breast cancer: trastuzumab deruxtecan(DS-8201a) and (Vic-)trastuzumab duocarmazine (SYD985)[J]. Eur J Med Chem, 2019, 183: 111682. DOI: 10.1016/j.ejmech.2019.111682. doi: 10.1016/j.ejmech.2019.111682
[12]	Ogitani Y, Aida T, Hagihara K, et al. DS-8201a, a novel HER2-targeting ADC with a novel DNA topoisomerase Ⅰ inhibitor, de-monstrates a promising antitumor efficacy with differentiation from T-DM1[J]. Clin Cancer Res, 2016, 22(20): 5097-5108. DOI: 10.1158/1078-0432.CCR-15-2822. doi: 10.1158/1078-0432.CCR-15-2822 pmid: 27026201
[13]	Tsurutani J, Iwata H, Krop I, et al. Targeting HER2 with trastuzumab deruxtecan: a dose-expansion, phase Ⅰ study in multiple advanced solid tumors[J]. Cancer Discov, 2020, 10(5): 688-701. DOI: 10.1158/2159-8290.CD-19-1014. doi: 10.1158/2159-8290.CD-19-1014 pmid: 32213540
[14]	Li BT, Smit EF, Goto Y, et al. Trastuzumab deruxtecan in HER2-mutant non-small-cell lung cancer[J]. N Engl J Med, 2022, 386(3): 241-251. DOI: 10.1056/NEJMoa2112431. doi: 10.1056/NEJMoa2112431
[15]	Li Q, Zhang R, Yan H, et al. Prognostic significance of HER3 in patients with malignant solid tumors[J]. Oncotarget, 2017, 8(40): 67140-67151. DOI: 10.18632/oncotarget.18007. doi: 10.18632/oncotarget.18007
[16]	Scharpenseel H, Hanssen A, Loges S, et al. EGFR and HER3 expression in circulating tumor cells and tumor tissue from non-small cell lung cancer patients[J]. Sci Rep, 2019, 9(1): 7406. DOI: 10.1038/s41598-019-43678-6. doi: 10.1038/s41598-019-43678-6 pmid: 31092882
[17]	Yonesaka K, Tanizaki J, Maenishi O, et al. HER3 augmentation via blockade of EGFR/AKT signaling enhances anticancer activity of HER3-targeting patritumab deruxtecan in EGFR-mutated non-small cell lung cancer[J]. Clin Cancer Res, 2022, 28(2): 390-403. DOI: 10.1158/1078-0432.CCR-21-3359. doi: 10.1158/1078-0432.CCR-21-3359
[18]	Schoenfeld AJ, Chan JM, Kubota D, et al. Tumor analyses reveal squamous transformation and off-target alterations as early resistance mechanisms to first-line osimertinib in EGFR-mutant lung cancer[J]. Clin Cancer Res, 2020, 26(11): 2654-2663. DOI: 10.1158/1078-0432.CCR-19-3563. doi: 10.1158/1078-0432.CCR-19-3563 pmid: 31911548
[19]	Jänne PA, Baik C, Su WC, et al. Efficacy and safety of patritumab deruxtecan (HER3-DXd) in EGFR inhibitor-resistant, EGFR-mutated non-small cell lung cancer[J]. Cancer Discov, 2022, 12(1): 74-89. DOI: 10.1158/2159-8290.CD-21-0715. doi: 10.1158/2159-8290.CD-21-0715
[20]	Ahmed Y, Berenguer-Pina JJ, Mahgoub T. The rise of the TROP2-targeting agents in NSCLC: new options on the horizon[J]. Onco-logy, 2021, 99(10): 673-680. DOI: 10.1159/000517438. doi: 10.1159/000517438
[21]	Goldenberg DM, Stein R, Sharkey RM. The emergence of trophoblast cell-surface antigen 2 (TROP-2) as a novel cancer target[J]. Oncotarget, 2018, 9(48): 28989-29006. DOI: 10.18632/oncotarget.25615. doi: 10.18632/oncotarget.25615 pmid: 29989029
[22]	Zaman S, Jadid H, Denson AC, et al. Targeting Trop-2 in solid tumors: future prospects[J]. Onco Targets Ther, 2019, 12: 1781-1790. DOI: 10.2147/OTT.S162447. doi: 10.2147/OTT.S162447
[23]	Okajima D, Yasuda S, Maejima T, et al. Datopotamab deruxtecan, a novel TROP2-directed antibody-drug conjugate, demonstrates potent antitumor activity by efficient drug delivery to tumor cells[J]. Mol Cancer Ther, 2021, 20(12): 2329-2340. DOI: 10.1158/1535-7163.MCT-21-0206. doi: 10.1158/1535-7163.MCT-21-0206
[24]	Meric-Bernstam F, Spira AI, Lisberg AE, et al. TROPION-PanTumor01: dose analysis of the TROP2-directed antibody-drug conjugate (ADC) datopotamab deruxtecan (Dato-DXd, DS-1062) for the treatment (Tx) of advanced or metastatic non-small cell lung cancer (NSCLC)[J]. J Clin Oncol, 2021, 39(15_suppl): 9058. DOI: 10.1200/JCO.2021.39.15_suppl.9058. doi: 10.1200/JCO.2021.39.15_suppl.9058
[25]	Seligson JM, Patron AM, Berger MJ, et al. Sacituzumab govitecan-hziy: an antibody-drug conjugate for the treatment of refractory, metastatic, triple-negative breast cancer[J]. Ann Pharmacother, 2021, 55(7): 921-931. DOI: 10.1177/1060028020966548. doi: 10.1177/1060028020966548 pmid: 33070624
[26]	Heist RS, Guarino MJ, Masters G, et al. Therapy of advanced non-small-cell lung cancer with an SN-38-anti-Trop-2 drug conjugate, sacituzumab govitecan[J]. J Clin Oncol, 2017, 35(24): 2790-2797. DOI: 10.1200/JCO.2016.72.1894. doi: 10.1200/JCO.2016.72.1894
[27]	Bylicki O, Paleiron N, Assié JB, et al. Targeting the MET-signaling pathway in non-small-cell lung cancer: evidence to date[J]. Onco Targets Ther, 2020, 13: 5691-5706. DOI: 10.2147/OTT.S219959. doi: 10.2147/OTT.S219959
[28]	Wang J, Anderson MG, Oleksijew A, et al. ABBV-399, a c-Met antibody-drug conjugate that targets both MET-amplified and c-Met-overexpressing tumors, irrespective of MET pathway dependence[J]. Clin Cancer Res, 2017, 23(4): 992-1000. DOI: 10.1158/1078-0432.CCR-16-1568. doi: 10.1158/1078-0432.CCR-16-1568
[29]	Strickler JH, Weekes CD, Nemunaitis J, et al. First-in-human phase Ⅰ, dose-escalation and -expansion study of telisotuzumab vedotin, an antibody-drug conjugate targeting c-Met, in patients with advanced solid tumors[J]. J Clin Oncol, 2018, 36(33): 3298-3306. DOI: 10.1200/JCO.2018.78.7697. doi: 10.1200/JCO.2018.78.7697 pmid: 30285518
[30]	Waqar SN, Redman MW, Arnold SM, et al. A phase Ⅱ study of telisotuzumab vedotin in patients with c-MET-positive stage Ⅳ or recurrent squamous cell lung cancer (LUNG-MAP sub-study S1400K, NCT03574753)[J]. Clin Lung Cancer, 2021, 22(3): 170-177. DOI: 10.1016/j.cllc.2020.09.013. doi: 10.1016/j.cllc.2020.09.013
[31]	Camidge DR, Barlesi F, Goldman JW, et al. A phase 1b study of telisotuzumab vedotin in combination with nivolumab in patients with NSCLC[J]. JTO Clin Res Rep, 2021, 3(1): 100262. DOI: 10.1016/j.jtocrr.2021.100262. doi: 10.1016/j.jtocrr.2021.100262
[32]	Camidge DR, Morgensztern D, Heist RS, et al. Phase Ⅰ study of 2- or 3-week dosing of telisotuzumab vedotin, an antibody-drug conjugate targeting c-Met, monotherapy in patients with advanced non-small cell lung carcinoma[J]. Clin Cancer Res, 2021, 27(21): 5781-5792. DOI: 10.1158/1078-0432.CCR-21-0765. doi: 10.1158/1078-0432.CCR-21-0765
[33]	Gazzah A, Bedard PL, Hierro C, et al. Safety, pharmacokinetics, and antitumor activity of the anti-CEACAM5-DM4 antibody-drug conjugate tusamitamab ravtansine (SAR408701) in patients with advanced solid tumors: first-in-human dose-escalation study[J]. Ann Oncol, 2022, 33(4): 416-425. DOI: 10.1016/j.annonc.2021.12.012. doi: 10.1016/j.annonc.2021.12.012