Trastuzumab Deruxtecan for the Treatment of HER2-positive Breast Cancer

Abstract

Trastuzumab deruxtecan (T-DXd) is a new-generation anti-human epidermal growth factor receptor 2 (HER2) antibody–drug conjugate that has demonstrated good efficacy due to its stable linker, high drug–antibody ratio, and high bystander effect resulting from the efficient cell membrane permeability of its payload. The DESTINY-Breast01 trial showed a response rate of >60% in patients with HER2-positive advanced recurrent breast cancer who had received a median of six regimens of prior therapy. The DESTINY-Breast03 trial, which compared T-DXd with trastuzumab emtansine (T-DM1) in HER2-positive unresectable and/or metastatic breast cancer also showed very high efficacy. Although T-DXd is highly effective, it is associated with a greater incidence of interstitial pneumonia than conventional anti-HER2 agents such as T-DM1. HER2-positive breast cancer frequently develops brain metastases, the drug therapy for which has had extremely limited success. Recently, however, in a small number of trials, T-DXd has been reported to be effective against brain metastasis, by shrinking BM.