Trastuzumab Deruxtecan Versus Trastuzumab Emtansine in HER2-Positive Breast Cancer: A Systematic Review of Efficacy, Safety, and Mechanisms
Sophia S. Lee
Mills High School, Millbrae, United States
Publication date: July 10, 2026
Mills High School, Millbrae, United States
Publication date: July 10, 2026
DOI: http://doi.org/10.34614/JIYRC2026I17
ABSTRACT
Human Epidermal Growth Factor Receptor 2 (HER2) targeting therapy is a key strategy used to treat breast cancer. Trastuzumab emtansine (T-DM1) is an antibody-drug conjugate (ADC) that consists of an anti-HER2 antibody conjugated with a tubulin inhibitor. Given the promising clinical outcomes of T-DM1, various payload-conjugated ADCs have been developed in clinical trials, including trastuzumab deruxtecan (T-Dxd). This systematic review examines the structural and functional differences between the two ADCs: cleavable vs non-cleavable linkers and tubulin inhibitor vs topoisomerase I inhibitor payloads. These distinct characters resulted in different clinical efficacy and safety, with T-Dxd demonstrating higher efficacy than T-DM1 by additionally targeting HER2-low cancers. Various combination partner trials, including immune checkpoint inhibitor (ICI), tyrosine kinase inhibitor (TKI), and pertuzumab, were examined when paired with T-Dxd or T-DM1. For T-Dxd, efficacy was more favorable in the combination therapy compared to that of monotherapy, unlike T-DM1, whose efficacy stayed constant throughout monotherapy and combination trials. This review provides a comprehensive examination of the effects of T-Dxd and T-DM1 in clinical trials, suggesting insight into future research in designing HER2-targeting-based therapy.
Human Epidermal Growth Factor Receptor 2 (HER2) targeting therapy is a key strategy used to treat breast cancer. Trastuzumab emtansine (T-DM1) is an antibody-drug conjugate (ADC) that consists of an anti-HER2 antibody conjugated with a tubulin inhibitor. Given the promising clinical outcomes of T-DM1, various payload-conjugated ADCs have been developed in clinical trials, including trastuzumab deruxtecan (T-Dxd). This systematic review examines the structural and functional differences between the two ADCs: cleavable vs non-cleavable linkers and tubulin inhibitor vs topoisomerase I inhibitor payloads. These distinct characters resulted in different clinical efficacy and safety, with T-Dxd demonstrating higher efficacy than T-DM1 by additionally targeting HER2-low cancers. Various combination partner trials, including immune checkpoint inhibitor (ICI), tyrosine kinase inhibitor (TKI), and pertuzumab, were examined when paired with T-Dxd or T-DM1. For T-Dxd, efficacy was more favorable in the combination therapy compared to that of monotherapy, unlike T-DM1, whose efficacy stayed constant throughout monotherapy and combination trials. This review provides a comprehensive examination of the effects of T-Dxd and T-DM1 in clinical trials, suggesting insight into future research in designing HER2-targeting-based therapy.
