Trastuzumab deruxtecan (ENHERTU®), a HER2-directed antibody and DNA 
topoisomerase I inhibitor conjugate, is being developed for the treatment of 
HER2-expressing solid tumours, including breast cancer, gastric cancer, 
colorectal cancer and non-small cell lung cancer by Daiichi Sankyo Company Ltd 
in collaboration with AstraZeneca. Based primarily on the results of the phase 2 
DESTINY-Breast01 trial, trastuzumab deruxtecan was recently approved in the USA 
under accelerated approval for the treatment of adult patients with unresectable 
or metastatic HER2-positive breast cancer who have received two or more prior 
anti-HER2-based regimens in the metastatic setting. This article summarizes the 
milestones in the development of trastuzumab deruxtecan leading to this first 
approval.