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中华临床医师杂志(电子版) ›› 2021, Vol. 15 ›› Issue (10) : 735 -739. doi: 10.3877/cma.j.issn.1674-0785.2021.10.004

所属专题: 乳腺疾病

专家论坛

HER2低表达乳腺癌及抗体偶联药物诊治进展
邬茜1, 辛灵1, 刘倩1, 刘荫华1,()   
  1. 1. 100034 北京,北京大学第一医院乳腺疾病中心
  • 收稿日期:2021-08-26 出版日期:2021-10-15
  • 通信作者: 刘荫华

Advances in diagnosis and treatment of HER2-low breast cancer and antibody drug conjugates

Qian Wu1, Ling Xin1, Qian Liu1, Yinhua Liu1,()   

  1. 1. Breast Disease Center, Peking University First Hospital, Beijing 100034, China
  • Received:2021-08-26 Published:2021-10-15
  • Corresponding author: Yinhua Liu
引用本文:

邬茜, 辛灵, 刘倩, 刘荫华. HER2低表达乳腺癌及抗体偶联药物诊治进展[J/OL]. 中华临床医师杂志(电子版), 2021, 15(10): 735-739.

Qian Wu, Ling Xin, Qian Liu, Yinhua Liu. Advances in diagnosis and treatment of HER2-low breast cancer and antibody drug conjugates[J/OL]. Chinese Journal of Clinicians(Electronic Edition), 2021, 15(10): 735-739.

DS-8201相关研究显示,经过多线解救治疗疾病进展的晚期人表皮生长因子受体2(HER2)低表达乳腺癌患者可以通过新型HER2抗体偶联药物(ADC)治疗达到临床显著获益。该结论不仅进一步细化了乳腺癌分类治疗理念,也引发了重新定义HER2表达状态标准的思考。同时,深入新型ADC药物研发工作正在成为新的热点问题而受到临床广泛关注。本文在复习HER2低表达乳腺癌研究历史及ADC药物研发现状的基础上,结合笔者研究数据,探讨HER2低表达乳腺癌临床病理特征及诊治进展。

Studies about DS-8201 have shown that patients who had advanced human epidermal growth factor receptor 2 (HER2)-low breast cancer refractory to standard therapies can achieve clinically significant benefits by novel HER2 antibody-drug conjugate (ADC). This conclusion not only further refines the classification of breast cancer, but also triggers the consideration of redefining the criteria for HER2 expression status. At the same time, in-depth research and development of novel ADCs is becoming a new hot issue and has received much clinical attention. In this paper, on the basis of reviewing the research history of HER2-low breast cancer and the current status of ADCs research and development, combined with our research data, we explore the clinicopathological features, diagnosis and treatment progress of HER2-low breast cancer.

表1 抗体偶联药物在HER2低表达乳腺癌中开展的相关临床试验
药物 试验号 分期 样本量(例) 人群 药物组合
DS-8201a NCT02564900 Ⅰb期 292 HER2阳性/低表达、晚期、后线 DS-8201a
DS-8201a NCT04132960 Ⅱ期 186 HER2过表达/低表达/无表达、晚期、后线 DS-8201a
DS-8201a NCT03734029(DESTINY-Breast04) Ⅲ期 557 HER2低表达、晚期、后线 DS-8201a vs 医生选择治疗(2∶1)
DS-8201a NCT04494425(DESTINY-Breast06) Ⅲ期 850 HER2低表达、激素受体阳性、晚期、后线 T-DXd vs 研究者选择化疗
DS-8201a NCT03523572 Ⅰb期 99 HER2阳性/低表达、晚期、后线 DS-8201a+纳武单抗
DS-8201a NCT04556773(DESTINY-Breast08) Ⅰb期 185 HER2低表达、晚期、后线

T-DXd+卡培他滨;

T-DXd+度伐单抗+紫杉醇;

T-DXd+Capivasertib;

T-DXd+阿那曲唑;

T-DXd+氟维司群

DS-8201a NCT04042701 Ⅰb期 115 HER2阳性/低表达、晚期、后线 T-DXd+帕博利珠单抗
DS-8201a NCT04553770 Ⅱ期 88 HER2低表达、激素受体阳性、早期、新辅助 DS-8201a vs DS-8201a+阿那曲唑
RC48-ADC NCT03052634 Ⅰb期 121 HER2阳性/低表达、晚期、后线 RC48-ADC
RC48-ADC NCT04400695 Ⅲ期 366 HER2低表达、晚期、后线 RC48-ADC vs 医生选择治疗
MRG002 NCT04742153 Ⅱ期 66 HER2低表达、晚期、后线 MRG002
SYD985 NCT02277717 Ⅰ期 185 HER2低表达、晚期、后线 SYD985
SYD985 NCT04602117 Ⅰ/Ⅰb期 27 HER2阳性或低表、晚期、后线 SYD985+紫杉醇
SYD985 NCT04235101 Ⅰ期 120 HER2阳性/低表达、晚期、后线 SYD985+尼拉帕利
ARX788 NCT02512237 Ⅰ期 80 HER2低表达、晚期、后线 ARX788
ARX788 NCT03255070 Ⅰ期 190 IHC 2+/ISH-、晚期、后线 ARX788
PF-06804103 NCT03284723 Ⅰ期 148 IHC 2+/ISH-、晚期、后线

PF-06804103;

PF-06804103+来曲唑+帕博西尼

FS-1502 NCT03944499 Ⅰ期 92 HER2低表达、晚期、后线 FS-1502
XMT-1522 NCT02952729 Ⅰ期 120 HER2低表达、晚期、后线 XMT-1522
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