“精准医疗”时代从乳腺癌分子分型探讨抗体-药物偶联物的临床价值及最新研究进展

doi:10.19401/j.cnki.1007-3639.2023.12.002

中国癌症杂志 ›› 2023, Vol. 33 ›› Issue (12): 1073-1082.doi: 10.19401/j.cnki.1007-3639.2023.12.002

“精准医疗”时代从乳腺癌分子分型探讨抗体-药物偶联物的临床价值及最新研究进展

王雪儿¹(), 王永胜²()

1.天津医科大学肿瘤医院肿瘤科，国家肿瘤临床医学研究中心，天津市肿瘤防治重点实验室，天津市恶性肿瘤临床医学研究中心，天津 300060
2.山东省肿瘤防治研究院（山东省肿瘤医院）乳腺病中心，山东第一医科大学（山东省医学科学院），山东济南 250117

收稿日期:2023-06-25 修回日期:2023-10-20 出版日期:2023-12-30 发布日期:2023-12-28
通信作者: 王永胜（ORCID: 0000-0001-6252-684X），主任医师，山东省肿瘤医院大外科主任兼乳腺病中心主任.
作者简介:王雪儿（ORCID: 0009-0004-0103-0655），博士。

The research advances and the clinical value of antibody-drug conjugate from molecular subtyping of breast cancer in the era of "precision medicine"

WANG Xueer¹(), WANG Yongsheng²()

1. Department of Oncology, Tianjin Medical University Cancer Institute and Hospital, National Clinical Research Center for Cancer, Key Laboratory of Cancer Prevention and Therapy, Tianjin’s Clinical Research Center for Cancer, Tianjin 300060, China
2. Department of Breast Cancer Center, Shandong Cancer Hospital and Institute, Shandong First Medical University and Shandong Academy of Medical Sciences, Jinan 250117, Shandong Province, China

Received:2023-06-25 Revised:2023-10-20 Published:2023-12-30 Online:2023-12-28
Contact: WANG Yongsheng.

摘要/Abstract

摘要：

乳腺癌的发病率目前已位居女性恶性肿瘤之首。乳腺癌具有高度异质性，可分为luminal A、luminal B、人类表皮生长因子受体2（human epidermal growth factor receptor 2，HER2）过表达及三阴性型4种分子分型。然而既往的分子分型方法导致处于HER2低表达状态患者的治疗选择十分有限。近年来，随着抗体-药物偶联物（antibody-drug conjugate，ADC）的飞速发展，使HER2低表达乳腺癌患者获得了新的治疗选择，并促进了当前国内外指南中对HER2表达状态判定标准的更新——基于免疫组化（immunohistochemistry，IHC）和原位杂交（in situ hybridization，ISH）检测技术，将HER2的表达分为HER2阳性（IHC 3+或IHC 2+/ISH+）、HER2低表达（IHC 1+或IHC 2+/ISH-）以及HER2阴性（IHC 0）3种情况。ADC是一种由连接子将单克隆抗体与细胞毒性物质偶联而成的免疫偶联物。在乳腺癌领域，多项大型临床试验已经证明了以HER2为靶点的ADC恩美曲妥珠单抗（T-DM1）、德曲妥珠单抗（T-DXd）以及以滋养层细胞表面抗原2（trophoblast cell surface antigen 2，TROP2）为靶点的ADC戈沙妥珠单抗在不同分子分型乳腺癌患者中的临床获益。随着DESTINY-Breast03等Ⅲ期临床试验发现T-DXd在晚期HER2阳性乳腺癌患者中的临床疗效优于T-DM1（完全缓解率约为T-DM1的2倍，中位无进展生存期约为T-DM1的4倍），T-DXd现今已经替代T-DM1成为HER2阳性乳腺癌二线治疗唯一推荐的药物，也是脑转移局部治疗后二线治疗的选择。Ⅲ期临床试验DESTINY-Breast04证实T-DXd同样可使HER2低表达的乳腺癌患者获益，这进一步改变了晚期乳腺癌的治疗格局，并支持重新定义HER2阴性乳腺癌分子亚型的必要。Ⅲ期临床试验ASCENT证实戈沙妥珠单抗可显著改善三阴性乳腺癌（triple-negative breast cancer，TNBC）患者的生存情况及生活质量，且Ⅱ期临床试验NeoSTAR发现该药在TNBC新辅助治疗中也可能具有良好的抗肿瘤作用。基于循证医学证据，目前T-DM1、T-DXd和戈沙妥珠单抗均已在国外和中国陆续获批上市。其他如HER3-DXd、Dato-DXd及中国研发的纬迪西妥单抗（RC48）等ADC药物也正在乳腺癌等肿瘤中广泛地开展临床研究。此外，尚有多种其他分子靶点的ADC仍正在积极地研发中。本文旨在从不同分子分型乳腺癌患者的ADC药物治疗出发，介绍最新的相关研究进展并探讨ADC在乳腺癌中的临床应用价值。

关键词: 乳腺癌, 分子分型, 人类表皮生长因子受体2, 抗体-药物偶联物

Abstract:

The incidence of breast cancer currently ranks first among malignant tumors in women. Breast cancer exhibits high heterogeneity and can be classified into four molecular subtypes: luminal A, luminal B, human epidermal growth factor receptor 2 (HER2) overexpression and triple-negative. However, previous molecular subtype classifications have limited treatment options for patients with HER2 low expression. In recent years, with the rapid development of antibody-drug conjugates (ADCs), new treatment options have emerged for breast cancer patients with HER2 low expression. This has also led to updates in the criteria for determining HER2 expression status in both domestic and international guidelines, based on immunohistochemistry (IHC) and in situ hybridization (ISH) testing, categorizing HER2 expression as HER2-positive (IHC 3+ or IHC 2+/ISH+), HER2 low expression (IHC 1+ or IHC 2+/ISH-),and HER2-negative (IHC 0). ADCs are immunotherapeutics composed of a linker that conjugates a monoclonal antibody with a cytotoxic payload. In the field of breast cancer, several large clinical trials have demonstrated clinical benefits of ADCs targeting HER2, such as trastuzumab emtansine (T-DM1), trastuzumab deruxtecan (T-DXd) and sacituzumab govitecan targeting trophoblast cell surface antigen 2 (TROP2), in various molecular subtypes of breast cancer. With the phase Ⅲ DESTINY-Breast03 trial and others, T-DXd has been found to have superior efficacy compared to T-DM1 in advanced HER2-positive breast cancer patients (approximately two times higher complete response rate, and four times longer median progression-free survival). T-DXd has now replaced T-DM1 as the recommended second-line therapy for HER2-positive breast cancer and as a second-line treatment option after local treatment for brain metastasis. The phase Ⅲ DESTINY-Breast04 trial confirmed that breast cancer patients with HER2 low expression can also benefit from T-DXd, further reshaping the treatment landscape for advanced breast cancer and supporting the need to redefine molecular subtypes of HER2-negative breast cancer. The phase Ⅲ ASCENT trial demonstrated that sacituzumab govitecan significantly improved survival and quality of life in triple-negative breast cancer (TNBC) patients, and the phase Ⅱ NeoSTAR study suggested its potential as neoadjuvant therapy in TNBC. Based on evidence, T-DM1, T-DXd and sacituzumab govitecan have been approved for marketing in both foreign and Chinese markets. Other ADC drugs, such as HER3-DXd, Dato-DXd and China-developed RC48, are also undergoing extensive clinical trials in the field of breast cancer and other tumors. Furthermore, there are several other ADCs targeting different molecular targets in active development. This article aimed to review the new advances related to ADCs therapy for breast cancer patients with different molecular subtypes and discuss the clinical application value of ADCs in breast cancer.

Key words: Breast cancer, Molecular typing, Human epidermal growth factor receptor 2, Antibody-drug conjugate

中图分类号:

R737.9

王雪儿, 王永胜. “精准医疗”时代从乳腺癌分子分型探讨抗体-药物偶联物的临床价值及最新研究进展[J]. 中国癌症杂志, 2023, 33(12): 1073-1082.

WANG Xueer, WANG Yongsheng. The research advances and the clinical value of antibody-drug conjugate from molecular subtyping of breast cancer in the era of "precision medicine"[J]. China Oncology, 2023, 33(12): 1073-1082.

图/表 2

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参考文献 52

[1]	World Health Organization. Global cancer observatory. Estimated number of new cases in 2020, World, both sexes, all ages[EB/OL]. 2020 [2022-11-10]. https://gco.iarc.fr/today/home.
[2]	周昌明, 王泽洲, 郑莹. 2023年美国癌症数据解读及对中国癌症防治的启示[J]. 中国癌症杂志, 2023, 33(2): 117-125. doi: 10.19401/j.cnki.1007-3639.2023.02.004
	ZHOU C M, WANG Z Z, ZHENG Y. Interpretation of US cancer statistics 2023 and its implications for cancer prevention and treatment in China[J]. China Oncol, 2023, 33(2): 117-125.
[3]	TARANTINO P, HAMILTON E, TOLANEY S M, et al. HER2-low breast cancer: pathological and clinical landscape[J]. J Clin Oncol, 2020, 38(17): 1951-1962. doi: 10.1200/JCO.19.02488 pmid: 32330069
[4]	WOLFF A C, HAMMOND M E H, ALLISON K H, et al. Human epidermal growth factor receptor 2 testing in breast cancer: American Society of Clinical Oncology/College of American Pathologists clinical practice guideline focused update[J]. J Clin Oncol, 2018, 36(20): 2105-2122. doi: 10.1200/JCO.2018.77.8738 pmid: 29846122
[5]	T-DXd: New standard for HER2-low breast cancer[J]. Cancer Discov, 2022, 12(8): 1828. doi: 10.1158/2159-8290.CD-NB2022-0043 pmid: 35666611
[6]	邬茜, 辛灵, 刘倩, 等. HER2低表达乳腺癌及抗体偶联药物诊治进展[J]. 中华临床医师杂志(电子版), 2021, 15(10): 735-739.
	WU Q, XIN L, LIU Q, et al. Advances in diagnosis and treatment of HER2-low breast cancer and antibody drug conjugates[J]. Chin J Clin Electron Ed, 2021, 15(10): 735-739.
[7]	中国抗癌协会乳腺癌专业委员会. 中国抗癌协会乳腺癌诊治指南与规范(2021年版)[J]. 中国癌症杂志, 2021, 31(10): 954-1040.
	The Society of Breast Cancer China Anti-Cancer Association. Guidelines for breast cancer diagnosis and treatment by China Anti-Cancer Association (2021 edition)[J]. China Oncol, 2021, 31(10): 954-1040.
[8]	JOUBERT N, BECK A, DUMONTET C, et al. Antibody-drug conjugates: the last decade[J]. Pharmaceuticals (Basel), 2020, 13(9): 245. doi: 10.3390/ph13090245
[9]	SCHLAM I, MOGES R, MORGANTI S, et al. Next-generation antibody-drug conjugates for breast cancer: moving beyond HER2 and TROP2[J]. Crit Rev Oncol Hematol, 2023, 190: 104090. doi: 10.1016/j.critrevonc.2023.104090
[10]	WANG J Y, LIU Y J, ZHANG Q Y, et al. RC48-ADC, a HER2-targeting antibody-drug conjugate, in patients with HER2-positive and HER2-low expressing advanced or metastatic breast cancer: a pooled analysis of two studies[J]. J Clin Oncol, 2021, 39(15_suppl): 1022. doi: 10.1200/JCO.2021.39.15_suppl.1022
[11]	BANYS-PALUCHOWSKI M, KRAWCZYK N, STICKELER E, et al. New treatment strategies for human epidermal growth factor receptor 2-positive breast cancer in 2023[J]. Curr Opin Obstet Gynecol, 2023, 35(1): 54-61. doi: 10.1097/GCO.0000000000000830
[12]	VON ARX C, DE PLACIDO P, CALTAVITURO A, et al. The evolving therapeutic landscape of trastuzumab-drug conjugates: future perspectives beyond HER2-positive breast cancer[J]. Cancer Treat Rev, 2023, 113: 102500. doi: 10.1016/j.ctrv.2022.102500
[13]	MODI S N, JACOT W, YAMASHITA T, et al. Trastuzumab deruxtecan in previously treated HER2-low advanced breast cancer[J]. N Engl J Med, 2022, 387(1): 9-20. doi: 10.1056/NEJMoa2203690
[14]	VERMA S, MILES D, GIANNI L, et al. Trastuzumab emtansine for HER2-positive advanced breast cancer[J]. N Engl J Med, 2012, 367(19): 1783-1791. doi: 10.1056/NEJMoa1209124
[15]	CORTÉS J, KIM S B, CHUNG W P, et al. Trastuzumab deruxtecan versus trastuzumab emtansine for breast cancer[J]. N Engl J Med, 2022, 386(12): 1143-1154. doi: 10.1056/NEJMoa2115022
[16]	HURVITZ S A, HEGG R, CHUNG W P, et al. Trastuzumab deruxtecan versus trastuzumab emtansine in patients with HER2-positive metastatic breast cancer: updated results from DESTINY-Breast03, a randomised, open-label, phase 3 trial[J]. Lancet, 2023, 401(10371): 105-117. doi: 10.1016/S0140-6736(22)02420-5
[17]	KROP I E, KIM S B, GONZÁLEZ-MARTÍN A, et al. Trastuzumab emtansine versus treatment of physician’s choice for pretreated HER2-positive advanced breast cancer (TH3RESA): a randomised, open-label, phase 3 trial[J]. Lancet Oncol, 2014, 15(7): 689-699. doi: 10.1016/S1470-2045(14)70178-0
[18]	EMENS L A, ESTEVA F J, BERESFORD M, et al. Trastuzumab emtansine plus atezolizumab versus trastuzumab emtansine plus placebo in previously treated, HER2-positive advanced breast cancer (KATE2): a phase 2, multicentre, randomised, double-blind trial[J]. Lancet Oncol, 2020, 21(10): 1283-1295. doi: S1470-2045(20)30465-4 pmid: 33002436
[19]	HURVITZ S A, DIRIX L, KOCSIS J, et al. Phase Ⅱ randomized study of trastuzumab emtansine versus trastuzumab plus docetaxel in patients with human epidermal growth factor receptor 2-positive metastatic breast cancer[J]. J Clin Oncol, 2013, 31(9): 1157-1163. doi: 10.1200/JCO.2012.44.9694
[20]	National Comprehensive Cancer Network. Clinical practice guidelines in oncology: breast cancer (version 4.2023) 2023[EB/OL]. https://www.nccn.org/professionals/physician_gls/pdf/breast.pdf.
[21]	RAMAKRISHNA N, ANDERS C K, LIN N U, et al. Management of advanced human epidermal growth factor receptor 2-positive breast cancer and brain metastases: ASCO guideline update[J]. J Clin Oncol, 2022, 40(23): 2636-2655.
[22]	GENNARI A, ANDRÉ F, BARRIOS C H, et al. ESMO clinical practice guideline for the diagnosis, staging and treatment of patients with metastatic breast cancer[J]. Ann Oncol, 2021, 32(12): 1475-1495. doi: 10.1016/j.annonc.2021.09.019 pmid: 34678411
[23]	BASELGA J, CORTÉS J, KIM S B, et al. Pertuzumab plus trastuzumab plus docetaxel for metastatic breast cancer[J]. N Engl J Med, 2012, 366(2): 109-119. doi: 10.1056/NEJMoa1113216
[24]	PEREZ E A, BARRIOS C, EIERMANN W, et al. Trastuzumab emtansine with or without pertuzumab versus trastuzumab plus taxane for human epidermal growth factor receptor 2-positive, advanced breast cancer: primary results from the phase Ⅲ MARIANNE study[J]. J Clin Oncol, 2017, 35(2): 141-148.
[25]	HURVITZ S, HEGG R, CHUNG W P, et al. Trastuzumab deruxtecan versus trastuzumab emtansine in patients with HER2-positive metastatic breast cancer: updated survival results of the randomized, phase 3 study DESTINY-Breast03[J]. Cancer Res, 2023, 83(5_Supplement): GS2-2.
[26]	SAURA C, OLIVEIRA M, FENG Y H, et al. Neratinib plus capecitabine versus lapatinib plus capecitabine in HER2-positive metastatic breast cancer previously treated with ≥ 2 HER2-directed regimens: phase Ⅲ NALA trial[J]. J Clin Oncol, 2020, 38(27): 3138-3149. doi: 10.1200/JCO.20.00147
[27]	MURTHY R K, LOI S, OKINES A, et al. Tucatinib, trastuzumab, and capecitabine for HER2-positive metastatic breast cancer[J]. N Engl J Med, 2020, 382(7): 597-609. doi: 10.1056/NEJMoa1914609
[28]	JACOBSON A. Trastuzumab deruxtecan improves progression-free survival and intracranial response in patients with HER2-positive metastatic breast cancer and brain metastases[J]. Oncologist, 2022, 27(Suppl 1): S3-S4. doi: 10.1093/oncolo/oyac009
[29]	BARTSCH R, BERGHOFF A S, FURTNER J, et al. Trastuzumab deruxtecan in HER2-positive breast cancer with brain metastases: a single-arm, phase 2 trial[J]. Nat Med, 2022, 28(9): 1840-1847. doi: 10.1038/s41591-022-01935-8 pmid: 35941372
[30]	PÉREZ-GARCÍA J M, VAZ BATISTA M, CORTEZ P, et al. Trastuzumab deruxtecan in patients with central nervous system involvement from HER2-positive breast cancer: the DEBBRAH trial[J]. Neuro Oncol, 2023, 25(1): 157-166. doi: 10.1093/neuonc/noac144
[31]	YAMANAKA T, NIIKURA N, NOMURA H, et al. Trastuzumab deruxtecan for the treatment of patients with HER2-positive breast cancer with brain and/or leptomeningeal metastases: a multicenter retrospective study (ROSET-BM study)[J]. Cancer Res, 2023, 83(5_Supplement): PD7-1.
[32]	WYNN C S, TANG S C. Anti-HER2 therapy in metastatic breast cancer: many choices and future directions[J]. Cancer Metastasis Rev, 2022, 41(1): 193-209. doi: 10.1007/s10555-022-10021-x
[33]	SCHETTINI F, CHIC N, BRASÓ-MARISTANY F, et al. Clinical, pathological, and PAM50 gene expression features of HER2-low breast cancer[J]. NPJ Breast Cancer, 2021, 7(1): 1. doi: 10.1038/s41523-020-00208-2
[34]	MIGLIETTA F, GRIGUOLO G, BOTTOSSO M, et al. Evolution of HER2-low expression from primary to recurrent breast cancer[J]. NPJ Breast Cancer, 2021, 7(1): 137. doi: 10.1038/s41523-021-00343-4
[35]	PEIFFER D S, ZHAO F Y, CHEN N, et al. Clinicopathologic characteristics and prognosis of ERBB2-low breast cancer among patients in the national cancer database[J]. JAMA Oncol, 2023, 9(4): 500-510. doi: 10.1001/jamaoncol.2022.7476
[36]	HARBECK N, MODI S N, JACOT W, et al. Trastuzumab deruxtecan vs treatment of physician’s choice in patients with HER2-low unresectable and/or metastatic breast cancer: subgroup analyses from DESTINY-Breast04[J]. Cancer Res, 2023, 83(5_Supplement): P1-11.
[37]	NARAYAN P, DILAWARI A, OSGOOD C, et al. US food and drug administration approval summary: fam-trastuzumab deruxtecan-nxki for human epidermal growth factor receptor 2-low unresectable or metastatic breast cancer[J]. J Clin Oncol, 2023, 41(11): 2108-2116. doi: 10.1200/JCO.22.02447
[38]	RUGO H S, BARDIA A, MARMÉ F, et al. Sacituzumab govitecan in hormone receptor-positive/human epidermal growth factor receptor 2-negative metastatic breast cancer[J]. J Clin Oncol, 2022, 40(29): 3365-3376. doi: 10.1200/JCO.22.01002
[39]	KUMARI L, MISHRA L, PATEL P, et al. Emerging targeted therapeutic strategies for the treatment of triple-negative breast cancer[J]. J Drug Target, 2023: 1-19.
[40]	JEON Y, JO U, HONG J, et al. Trophoblast cell-surface antigen 2 (TROP2) expression in triple-negative breast cancer[J]. BMC Cancer, 2022, 22(1): 1014. doi: 10.1186/s12885-022-10076-7 pmid: 36153494
[41]	BARDIA A, HURVITZ S A, TOLANEY S M, et al. Sacituzumab govitecan in metastatic triple-negative breast cancer[J]. N Engl J Med, 2021, 384(16): 1529-1541. doi: 10.1056/NEJMoa2028485
[42]	LOIBL S, LOIRAT D, TOLANEY S M, et al. Health-related quality of life in the phase Ⅲ ASCENT trial of sacituzumab govitecan versus standard chemotherapy in metastatic triple-negative breast cancer[J]. Eur J Cancer, 2023, 178: 23-33. doi: 10.1016/j.ejca.2022.10.003
[43]	SPRING L, TOLANEY S, DESAI N, et al. Phase 2 study of response-guided neoadjuvant sacituzumab govitecan (IMMU-132) in patients with localized triple-negative breast cancer: results from the NeoSTAR trial[J]. J Clin Oncol, 2022, 40: 512-512.
[44]	JABBARZADEH KABOLI P, SHABANI S, SHARMA S, et al. Shedding light on triple-negative breast cancer with Trop2-targeted antibody-drug conjugates[J]. Am J Cancer Res, 2022, 12(4): 1671-1685. pmid: 35530278
[45]	BARDIA A, KROP I, MERIC-BERNSTAM F, et al. Datopotamab deruxtecan (dato-DXd) in advanced triple-negative breast cancer (TNBC): updated results from the phase 1 TROPION-PanTumor01 study[J]. Cancer Res, 2023, 83(5_Supplement): P6-10.
[46]	ANDRÉ F, HEE PARK Y, KIM S B, et al. Trastuzumab deruxtecan versus treatment of physician’s choice in patients with HER2-positive metastatic breast cancer (DESTINY-Breast02): a randomised, open-label, multicentre, phase 3 trial[J]. Lancet, 2023, 401(10390): 1773-1785. doi: 10.1016/S0140-6736(23)00725-0
[47]	DIECI M V, MIGLIETTA F, GRIGUOLO G, et al. Biomarkers for HER2-positive metastatic breast cancer: beyond hormone receptors[J]. Cancer Treat Rev, 2020, 88: 102064. doi: 10.1016/j.ctrv.2020.102064
[48]	KOYAMA K, ISHIKAWA H, ABE M, et al. Patritumab deruxtecan (HER3-DXd), a novel HER3 directed antibody drug conjugate, exhibits in vitro activity against breast cancer cells expressing HER3 mutations with and without HER2 overexpression[J]. PLoS One, 2022, 17(5): e0267027. doi: 10.1371/journal.pone.0267027
[49]	ALVES F R, GIL L, VASCONCELOS DE MATOS L, et al. Impact of human epidermal growth factor receptor 2 (HER2) low status in response to neoadjuvant chemotherapy in early breast cancer[J]. Cureus, 2022, 14(2): e22330.
[50]	TARANTINO P, JIN Q C, TAYOB N, et al. Prognostic and biologic significance of ERBB2-low expression in early-stage breast cancer[J]. JAMA Oncol, 2022, 8(8): 1177-1183. doi: 10.1001/jamaoncol.2022.2286 pmid: 35737367
[51]	CHERIFI F, DA SILVA A, JOHNSON A, et al. HELENA: HER2-Low as a prEdictive factor of response to Neoadjuvant chemotherapy in eArly breast cancer[J]. BMC Cancer, 2022, 22(1): 1081. doi: 10.1186/s12885-022-10163-9 pmid: 36266623
[52]	WOLFF A C, SOMERFIELD M R, DOWSETT M, et al. Human epidermal growth factor receptor 2 testing in breast cancer: ASCO-College of American Pathologists guideline update[J]. J Clin Oncol, 2023, 41(22): 3867-3872. doi: 10.1200/JCO.22.02864

Study drug	Study name	Clinical staging	HER2 status of study population	Treatment protocol/ number of lines	Primary efficacy endpoint	Safety
T-DXd	DESTINY-Breast01^[13]	Phase Ⅱ	Positive HER2	T-DXd Second-line and late-line therapy	ORR: 60.9%	AE: 99.5% ≥Grade 3 AE: 57.1%
	DESTINY-Breast02^[46]	Phase Ⅲ		T-DXd vs capecitabine + trastuzumab/lapatinib selected by clinicians Third-line therapy	Median PFS evaluated by BICR: 17.8 months vs 6.9 months (P<0.000)	TEAE: >99% vs 95% ≥Grade 3 TEAE: 53% vs 44%
	DESTINY-Breast03^[16]	Phase Ⅲ		T-DXd vs TDM1 Second-line and late-line therapy	Median PFS evaluated by BICR: 28.8 months vs 6.8 months (P<0.000)	TEAE: >99% vs 95% ≥Grade 3 TEAE: 56% vs 52%
T-DXd	DESTINY-Breast04^[13]	Phase Ⅲ	Low HER2 expression	T-DXd vs routine chemotherapy Second-line and late-line therapy	Median PFS: 10.1 months vs 5.4 months	AE: 99.5% vs 98.3% ≥Grade 3 AE: 52.6% vs 67.4%
Sacituzumab govitecan	TROPiCS-02^[38]	Phase Ⅲ	Negative HER2	Ditto Third-line and late-line therapy	Median PFS evaluated by BICR: 5.5 months vs 4.0 months (P=0.001)	Important ≥Grade 3 TEAE: Neutropenia: 51% vs 38% Diarrhea: 9% vs 1%
	ASCENT^[41]	Phase Ⅲ		Sacituzumab govitecan vs capecitabine, eribulin, vinorelbine or gemcitabine selected by clinicians Third-line and post-line therapy	Median PFS evaluated by BICR PFS: 5.6 months vs 1.7 months (P<0.001)	AE: 98% vs 86% Grade 3/4 AE: 64% vs 47%

Target/study drug	Trial/study name	Clinical staging/study design	Study population	Treatment protocol	Status
HER3/patritumab deruxtecan（HER3-DXd, U3-1402）	NCT04610528/TOT-HER3	Phase Ⅰ/single group assignment	HR+/HER2- early breast cancer	U3-1402	Active, not recruiting
Nectin4/enfortumab vedotin（EV, ASG-22CE）	NCT04225117/EV-202	Phase Ⅱ/parallel assignment	Locally advanced or metastatic malignant solid tumors (including HR+/HER2- breast cancer; TNBC)	ASG-22CE	Active, not recruiting
LIV-1/ladiratuzumab vedotin（SGN-LIV1A）	NCT03310957	Phase Ⅰb, Ⅱ/single group Assignment	TNBC	SGN-LIV1A + pembrolizumab	Active, not recruiting
ROR2/CAB-ROR2-ADC (BA3021)	NCT03504488	Phase Ⅰ, Ⅱ/RCT	Solid tumors (including TNBC)	BA3021 vs BA3021 + PD-1 inhibitor	Recruiting
TROP2/datopotamab deruxtecan (Dato-DXd)	NCT05460273/TROPION-PanTumor02	Phase Ⅰ, Ⅱ/single group assignment	TNBC; NSCLC	Dato-DXd	Active, not recruiting
TROP2/SKB264	NCT04152499	Phase Ⅰ, Ⅱ/sequential assignment	Advanced unresectable/metastatic solid tumors (including HR+/HER2- breast cancer; TNBC)	SKB264	Recruiting
Tubulin tissue factor/XB-002	NCT04925284/JEWEL-101	Phase Ⅰ/RCT	Advanced solid tumors (including HR+ breast cancer, TNBC)	XB-002 ± nivolumab/bevacizumab	Recruiting
FRɑ/farletuzumab ecteribulin	NCT04300556	Phase Ⅰ, Ⅱ/sequential assignment	Solid tumor (including TNBC)	Farletuzumab ecteribulin	Recruiting

“精准医疗”时代从乳腺癌分子分型探讨抗体-药物偶联物的临床价值及最新研究进展

The research advances and the clinical value of antibody-drug conjugate from molecular subtyping of breast cancer in the era of "precision medicine"

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