Sacituzumab govitecan and trastuzumab deruxtecan: two new antibody–drug conjugates in the breast cancer treatment landscape

ESMO Open

article

E. Adams¹  H. Wildiers²  P. Neven⁴  K. Punie² 

[1] Department of General Internal Medicine, University Hospitals Leuven;Department of General Medical Oncology and Multidisciplinary Breast Centre, Leuven Cancer Institute, University Hospitals Leuven;Laboratory of Experimental Oncology, Department of Oncology;Department of Gynaecology/Obstetrics and Multidisciplinary Breast Centre, Leuven Cancer Institute, University Hospitals Leuven;Gynaecological Oncology, Department of Oncology

关键词: antibody–drug conjugates;    sacituzumab govitecan;    trastuzumab deruxtecan;    HER2-positive breast cancer;    triple-negative breast cancer;   

DOI  :  10.1016/j.esmoop.2021.100204

学科分类：社会科学、人文和艺术（综合）

来源: BMJ Publishing Group

【 摘 要 】

Background Two new antibody–drug conjugates (ADCs) containing a topoisomerase I inhibitor payload have recently emerged in the breast cancer (BC) treatment landscape. Sacituzumab govitecan-hziy (SG) is a first-in-class anti-trophoblast cell-surface antigen 2 ADC approved for pretreated metastatic triple-negative breast cancer (mTNBC) and trastuzumab deruxtecan (T-DXd) gained approval for human epidermal growth factor receptor-2 (HER2)-positive advanced BC (aBC). We aim to provide a contemporary review and the current clinical trial landscape of SG and T-DXd in BC.Materials and methods We conducted a literature search from Medline database through PubMed, major conference proceedings [abstracts from European Society for Medical Oncology (Breast) Congress, American Society of Clinical Oncology annual meeting, San Antonio Breast Cancer Symposium] and ClinicalTrials.gov with search terms ‘sacituzumab govitecan', ‘IMMU-132', ‘trastuzumab deruxtecan' and ‘DS-8201a' up to 21 March 2021.Results We assessed 293 records for eligibility, of which 153 were included in this review after screening and exclusion. For SG, efficacy and safety data are available from a phase III trial in pretreated mTNBC and from a phase I/II basket study in mTNBC and hormone receptor-positive/HER2-negative aBC. Thirteen trials with pending primary analysis are ongoing with SG as single agent or in combination, of which 11 are enrolling (2/11 in the early setting). For T-DXd, efficacy/safety data are available as single agent in pretreated HER2-positive (phase Ib and phase II) and in HER2-low aBC (phase Ib), and in combination with nivolumab in HER2-low/positive aBC (phase Ib). Of 23 ongoing trials with T-DXd, 12 are open for enrollment and 3 phase III trials have completed recruitment. The distinct safety profiles of both drugs and their management are discussed.Conclusion Given their robust single-agent activity, SG and T-DXd are expected to substantially impact treatment standards, both in and far beyond the currently approved indications. Several trials are investigating new treatment settings for both drugs, including a transition to earlier lines and combinations with other anticancer treatments such as immune checkpoint inhibitors.

【 授权许可】

CC BY|CC BY-NC-ND