| Citation: |
ZHANG Liang, YANG Changliang, LI Peidong, CHENG Ying. Progress of Research on Advanced Non-Small Cell Lung Cancer with HER-2 Mutation[J]. Cancer Research on Prevention and Treatment, 2025, 52(2): 87-92. DOI: 10.3971/j.issn.1000-8578.2025.24.1062
|
Anti-tumor drug research and development in non-small cell lung cancer (NSCLC) is rapidly developing, and the clinical application of high-throughput sequencing technology is also becoming widespread. Accordingly, researchers are focusing on human epidermal growth factor receptor-2 (HER-2) gene as a rare target of NSCLC, and a series of exploratory studies has been performed. Traditional chemotherapy and immunotherapy are unsatisfactory in the HER-2 mutant population, whereas the survival improvement of anti-HER-2 monoclonal antibodies and pan-HER inhibitors is limited. The development of antibody drug conjugate (ADC) ushers in a turning point for HER-2-mutated NSCLC, and new ADC drugs represented by trastuzumab deruxtecan are making a breakthrough. It opens up a new era of precision therapy for advanced HER-2-mutated NSCLC. Additionally, novel HER-2 inhibitors show very encouraging initial efficacy and safety, and clinical trials are ongoing. This review focuses on the latest progress of research on HER-2-mutated NSCLC.
Competing interests: The authors declare that they have no competing interests.
| [1] |
Tomizawa K, Suda K, Onozato R, et al. Prognostic and predictive implications of HER2/ERBB2/neu gene mutations in lung cancers[J]. Lung Cancer, 2011, 74(1): 139-144. doi: 10.1016/j.lungcan.2011.01.014
|
| [2] |
Liu L, Shao X, Gao W, et al. The role of human epidermal growth factor receptor 2 as a prognostic factor in lung cancer: a meta-analysis of published data[J]. J Thorac Oncol, 2010, 5(12): 1922-1932. doi: 10.1097/JTO.0b013e3181f26266
|
| [3] |
Hirsch FR, Varella-Garcia M, Franklin WA, et al. Evaluation of HER-2/neu gene amplification and protein expression in non-small cell lung carcinomas[J]. Br J Cancer, 2002, 86(9): 1449-1456. doi: 10.1038/sj.bjc.6600286
|
| [4] |
Pillai RN, Behera M, Berry LD, et al. HER2 mutations in lung adenocarcinomas: A report from the Lung Cancer Mutation Consortium[J]. Cancer, 2017, 123(21): 4099-4105. doi: 10.1002/cncr.30869
|
| [5] |
Jing C, Mao X, Wang Z, et al. Next-generation sequencing-based detection of EGFR, KRAS, BRAF, NRAS, PIK3CA, Her-2 and TP53 mutations in patients with non-small cell lung cancer[J]. Mol Med Rep, 2018, 18(2): 2191-2197.
|
| [6] |
Wen S, Dai L, Wang L, et al. Genomic Signature of Driver Genes Identified by Target Next-Generation Sequencing in Chinese Non-Small Cell Lung Cancer[J]. Oncologist, 2019, 24(11): e1070-e1081. doi: 10.1634/theoncologist.2018-0572
|
| [7] |
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
|
| [8] |
Yang G, Yang Y, Liu R, et al. First-line immunotherapy or angiogenesis inhibitor plus chemotherapy for HER2-altered NSCLC: a retrospective real-world POLISH study[J]. Ther Adv Med Oncol, 2022, 14: 17588359221082339.
|
| [9] |
Nagano M, Kohsaka S, Ueno T, et al. High-Throughput Functional Evaluation of Variants of Unknown Significance in ERBB2[J]. Clin Cancer Res, 2018, 24(20): 5112-5122. doi: 10.1158/1078-0432.CCR-18-0991
|
| [10] |
Zhang S, Wang W, Xu C, et al. Chinese expert consensus on the diagnosis and treatment of HER2-altered non-small cell lung cancer[J]. Thorac Cancer, 2023, 14(1): 91-104. doi: 10.1111/1759-7714.14743
|
| [11] |
Mazières J, Barlesi F, Filleron T, et al. Lung cancer patients with HER2 mutations treated with chemotherapy and HER2-targeted drugs: results from the European EUHER2 cohort[J]. Ann Oncol, 2016, 27(2): 281-286. doi: 10.1093/annonc/mdv573
|
| [12] |
Wang Y, Zhang S, Wu F, et al. Outcomes of Pemetrexed-based chemotherapies in HER2-mutant lung cancers[J]. BMC Cancer, 2018, 18(1): 326. doi: 10.1186/s12885-018-4277-x
|
| [13] |
Li J, Xie M, Zhao R, et al. Anti-angiogenic therapy or immunotherapy? A real-world study of patients with advanced non-small cell lung cancer with EGFR/HER2 exon 20 insertion mutations[J]. Front Oncol, 2024, 14: 1357231. doi: 10.3389/fonc.2024.1357231
|
| [14] |
Kato Y, Udagawa H, Matsumoto S, et al. Efficacy of immune checkpoint inhibitors plus platinum-based chemotherapy as 1st line treatment for patients with non-small cell lung cancer harboring HER2 mutations: Results from LC-SCRUM-Asia[J]. Lung Cancer, 2024, 197: 107992. doi: 10.1016/j.lungcan.2024.107992
|
| [15] |
Saalfeld FC, Wenzel C, Christopoulos P, et al. Efficacy of Immune Checkpoint Inhibitors Alone or in Combination With Chemotherapy in NSCLC Harboring ERBB2 Mutations[J]. J Thorac Oncol, 2021, 16(11): 1952-1958. doi: 10.1016/j.jtho.2021.06.025
|
| [16] |
Mazieres J, Drilon A, Lusque A, et al. Immune checkpoint inhibitors for patients with advanced lung cancer and oncogenic driver alterations: results from the IMMUNOTARGET registry[J]. Ann Oncol, 2019, 30(8): 1321-1328. doi: 10.1093/annonc/mdz167
|
| [17] |
Guisier F, Dubos-Arvis C, Viñas F, et al. 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[J]. J Thorac Oncol, 2020, 15(4): 628-636. doi: 10.1016/j.jtho.2019.12.129
|
| [18] |
Kinoshita I, Goda T, Watanabe K, et al. A phase II study of trastuzumab monotherapy in pretreated patients with non-small cell lung cancers (NSCLCs) harboring HER2 alterations: HOT1303-B trial[J], Ann Oncol, 2018, 29: viii540.
|
| [19] |
Hainsworth JD, Meric-Bernstam F, Swanton C, et al. Targeted Therapy for Advanced Solid Tumors on the Basis of Molecular Profiles: Results From MyPathway, an Open-Label, Phase IIa Multiple Basket Study[J]. J Clin Oncol, 2018, 36(6): 536-542. doi: 10.1200/JCO.2017.75.3780
|
| [20] |
Mazieres J, Lafitte C, Ricordel C, et al. 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[J]. J Clin Oncol, 2022, 40(7): 719-728. doi: 10.1200/JCO.21.01455
|
| [21] |
De Grève J, Moran T, Graas MP, et al. Phase II study of afatinib, an irreversible ErbB family blocker, in demographically and genotypically defined lung adenocarcinoma[J]. Lung Cancer, 2015, 88(1): 63-69. doi: 10.1016/j.lungcan.2015.01.013
|
| [22] |
Kris MG, Camidge DR, Giaccone G, et al. Targeting 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[J]. Ann Oncol, 2015, 26(7): 1421-1427. doi: 10.1093/annonc/mdv186
|
| [23] |
Hyman DM, Piha-Paul SA, Won H, et al. HER kinase inhibition in patients with HER2- and HER3-mutant cancers[J]. Nature, 2018, 554(7691): 189-194. doi: 10.1038/nature25475
|
| [24] |
Gandhi L, Besse B, Mazieres J, et al. MA04.02 neratinib ± temsirolimus in HER2-mutant lung cancers: an international, randomized phase Ⅱ study[J]. J Thorac Oncol, 2017, 12(1): S358-S359. doi: 10.1016/j.jtho.2016.11.398
|
| [25] |
Le X, Cornelissen R, Garassino M, et al. Poziotinib in Non-Small-Cell Lung Cancer Harboring HER2 Exon 20 Insertion Mutations After Prior Therapies: ZENITH20-2 Trial[J]. J Clin Oncol, 2022, 40(7): 710-718. doi: 10.1200/JCO.21.01323
|
| [26] |
Cornelissen R, Prelaj A, Sun S, et al. Poziotinib in Treatment-Naive NSCLC Harboring HER2 Exon 20 Mutations: ZENITH20-4, A Multicenter, Multicohort, Open-Label, Phase 2 Trial (Cohort 4)[J]. J Thorac Oncol, 2023, 18(8): 1031-1041. doi: 10.1016/j.jtho.2023.03.016
|
| [27] |
Zhou C, Li X, Wang Q. Pyrotinib in HER2-mutant advanced lung adenocarcinoma after platinum-based chemotherapy: a multicenter, open-label, single-arm, phase Ⅱ study[J]. J Clin Oncol, 2020, 38(24): 2753-2761. doi: 10.1200/JCO.20.00297
|
| [28] |
Li BT, Smit EF, Goto Y, et al. DESTINY-Lung01 Trial Investigators. Trastuzumab Deruxtecan in HER2-Mutant Non-Small-Cell Lung Cancer[J]. N Engl J Med, 2022, 386(3): 241-251. doi: 10.1056/NEJMoa2112431
|
| [29] |
Goto K, Goto Y, Kubo T, et al. Trastuzumab Deruxtecan in Patients With HER2-Mutant Metastatic Non-Small-Cell Lung Cancer: Primary Results From the Randomized, Phase Ⅱ DESTINY-Lung02 Trial[J]. J Clin Oncol, 2023, 41(31): 4852-4863. doi: 10.1200/JCO.23.01361
|
| [30] |
Li BT, Planchard D, Goto K, et al. Trastuzumab deruxtecan (T-DXd) in patients (pts) with HER2(ERBB2)-mutant (HER2m) metastatic nonesmall cell lung cancer (NSCLC) with and without brain metastases (BMs): Pooled analyses from DESTINY-Lung01 and DESTINYLung02[J]. Ann Oncol, 2023, 34(suppl_2): S755-S851.
|
| [31] |
Cheng Y, Wu L, Fang Y, et al. Trastuzumab deruxtecan (T-DXd) in Chinese patients (pts) with previously treated HER2 mutant non-small cell lung cancer (NSCLC): primary analysis from the Phase 2 DESTINY-Lung05 (DL-05) trial[J]. Cancer Res, 2024, 84(suppl_7): Abstract CT248.
|
| [32] |
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
|
| [33] |
Li Z, Song Z, Hong W, et al. SHR-A1811 (antibody-drug conjugate) in advanced HER2-mutant non-small cell lung cancer: a multicenter, open-label, phase 1/2 study[J]. Signal Transduct Target Ther, 2024, 9(1): 182. doi: 10.1038/s41392-024-01897-y
|
| [34] |
Zhou CC, Yang B, Sun Y, et al. Preliminary Results from A FIH Study of GQ1005, A Novel HER2-ADC, in Patients with Advanced HER2-expressing Solid Tumors And HER2-mutated NSCLC[J]. J Thorac Oncol, 2024, 19(suppl_10): S46.
|
| [35] |
Kim TM, Kim HR, Herbert H, et al. Safety and anti-tumor activity of BAY 2927088 in patients with HER2-mutant NSCLC: Results from an expansion cohort of the SOHO-01 phase Ⅰ/Ⅱ study[J]. J Clin Oncol, 2024, 42(suppl_17): LBA8598.
|
| [36] |
Le XN, Girard N, Jänne PA, et al. Safety and Efficacy of BAY 2927088 In Patients with HER2-Mutant NSCLC: Expansion Cohort from the Phase Ⅰ/Ⅱ SOHO-01 Study[J]. J Thorac Oncol, 2024, 19(suppl_10): S4.
|
| [37] |
Heymach J, Opdam F, Barve MA, et al. Phase Ia/Ib trial of zongertinib (BI 1810631), a HER2-specific tyrosine kinase inhibitor (TKI), in patients (pts) with HER2 aberration-positive solid tumors: Updated Phase Ia data from Beamion LUNG-1, including progression-free survival (PFS) data[J]. J Clin Oncol, 2024, 42(suppl_16): 8514.
|
| [38] |
Ruiter G, Tu HY, Ahn MJ, et al. Primary Phase Ⅰb Analysis of Beamion LUNG-1: Zongertinib (BI 1810631) in Patients with HER2 Mutation-Positive NSCLC[J]. J Thorac Oncol, 2024, 19(suppl_10): S4-S5.
|
| [1] | YANG Li, SHI Gaofeng, LIU Hui, ZHOU Tao. Correlation on MRI Features and HER-2 Expression of Breast Cancer[J]. Cancer Research on Prevention and Treatment, 2013, 40(11): 1070-1073. DOI: 10.3971/j.issn.1000-8578.2013.11.013 |
| [2] | WANG Ping, LIU Jing, HE Huiming, SU Meifang, HU Guoqing. Relationship between HER-2, Anemia, Prealbumin and Prognosis of Gastric Cancer[J]. Cancer Research on Prevention and Treatment, 2013, 40(05): 439-443. DOI: 10.3971/j.issn.1000-8578.2013.05.007 |
| [3] | WU Xin-hong, FENG Yao-jun, PAN Cui-ping, XU Juan, ZHONG Wei, SHAO Jun, MA Biao. Alteration of Biomarker HER-2 between Pre-and Post-neoadjuvant Chemotherapy in Breast Cancer Patients[J]. Cancer Research on Prevention and Treatment, 2011, 38(08): 930-932. DOI: 10.3971/j.issn.1000-8578.2011.08.019 |
| [4] | SONG Bao, ZHENG Gang, XIE Li, WEI Ling, WANG Xing-wu, LV Li-yan, SONG Xian-rang, ZUO Wen-shu. HER-2 Expression in Breast Cancer Tissues and Metastasis Lymph Nodes and Comparative Study in Detection Methods[J]. Cancer Research on Prevention and Treatment, 2011, 38(01): 70-7072. DOI: 10.3971/j.issn.1000-8578.2011.01.020 |
| [5] | LU Hao-yuan, BAI Xian-zhong. Expression of Cyclooxygenase-2 (COX-2)in Human Transitional Cell Carcinoma of Bladder and Its Relationship with HER-2 and p53[J]. Cancer Research on Prevention and Treatment, 2010, 37(05): 558-561. DOI: 10.3971/j.issn.1000-8578.2010.05.019 |
| [6] | HAO Tong-li, XIAO Xu-ren, GUO Gang, ZHU Jie. Targeting HER-2 Signal Pathway in LNCaP Prostate Cancer Cells by Sodium Butyrate[J]. Cancer Research on Prevention and Treatment, 2008, 35(07): 476-478. DOI: 10.3971/j.issn.1000-8578.1868 |
| [7] | LV Ya-li, ZHONG Mei, ZHAO Po. Application of Fluorescent in Situ Hybridization ( FISH) to Detect the Amplification of HER-2 Gene in Paraff in Sample of Breast Cancer[J]. Cancer Research on Prevention and Treatment, 2007, 34(05): 345-347. DOI: 10.3971/j.issn.1000-8578.2388 |
| [8] | ZHOU Ying, LING Bin, GAO Ting, CHEN Min, FENG Ding-qing, CHENG Zhi-xiang, ZHU Yuan-yuan, ZHAO Wei-dong, SHI Yong-yun, WANG Mei-mei, ZHU Huai-ping. Construction of Recombinant Retroviral Vector of siRNA Specific for Her-2 and the Expression of Recombinant Vector in SKOV3[J]. Cancer Research on Prevention and Treatment, 2007, 34(04): 277-280. DOI: 10.3971/j.issn.1000-8578.301 |
| [9] | WU Feng, WANG Qing-ming, FAN Guo-cai, CHEN Ji-zhong, CHEN Hui-peng. The Inhibition of HER-2 Expression by siRNA[J]. Cancer Research on Prevention and Treatment, 2006, 33(04): 215-218，. DOI: 10.3971/j.issn.1000-8578.423 |
| [10] | XIONG Hui-hua, YU Shi-ying, XIA Shu, ZHUANG Liang. The Expression of survivin and Its Relationship with The Expression of Mutant p53, HER-2 in Breast Carcinoma[J]. Cancer Research on Prevention and Treatment, 2005, 32(11): 707-709. DOI: 10.3971/j.issn.1000-8578.2221 |
This work is licensed under a Creative Commons Attribution 3.0 License.
Copyright © Editorial Department of Cancer Prevention Research 鄂公网安备 42011102005013号 鄂ICP备2022015867号
Supported by: Beijing Renhe Information Technology Co., Ltd. 
DownLoad: