Trastuzumab deruxtecan in HER2-positive metastatic breast cancer and beyond

INTRODUCTION: Despite the substantial improvements made in human epidermal growth factor receptor 2 (HER2)-targeted therapies since the approval of trastuzumab more than 20 years ago, there is still considerable unmet need in patients with HER2-expressing breast cancer (BC) and other solid tumors. Trastuzumab deruxtecan (T-DXd) is a newer antibody-drug conjugate approved for the treatment of metastatic breast cancer (BC) and gastric cancer (GC) and is under active investigation in other solid tumors, including non-small cell lung cancer, colorectal cancer, and HER2-low tumors. AREAS COVERED: The current treatment and investigational landscape of HER2-positive and HER2-low metastatic BC (mBC) and the preclinical and clinical trials investigating T-DXd. To identify relevant literature, a search was performed on English-language publications and congress abstracts. EXPERT OPINION: T-DXd is likely to become the standard of care for second-line treatment of HER2-positive mBC, and it may play a role in the treatment of hormone receptor-positive and triple-negative mBC with HER2-low expression. Because it was recently approved in the United States and Japan to treat HER2-positive metastatic GC, it holds promise for the treatment of other HER2-positive solid tumors, including colorectal cancer, non-small cell lung cancer, and HER2-low BC.