
Trastuzumab deruxtecan for the treatment of patients with HER2-positive gastric cancer
Author(s) -
Daisuke Kotani,
Kohei Shitara
Publication year - 2021
Publication title -
therapeutic advances in medical oncology
Language(s) - English
Resource type - Journals
SCImago Journal Rank - 2.272
H-Index - 49
eISSN - 1758-8359
pISSN - 1758-8340
DOI - 10.1177/1758835920986518
Subject(s) - medicine , trastuzumab , cancer , oncology , antibody , clinical endpoint , clinical trial , immunology , breast cancer
Trastuzumab deruxtecan (T-DXd) is a novel anti-human epidermal growth factor receptor 2 (HER2) antibody–drug conjugate composed of a monoclonal anti-HER2 antibody and a topoisomerase I inhibitor, DX-8951 derivative (an exatecan derivative). T-DXd showed potential anti-tumor activities in HER2-positive gastric cancer cell lines and xenograft models. In the randomized, phase II trial DESTINY-Gastric01, T-DXd demonstrated a significantly higher objective response rate as a primary endpoint and a longer overall survival as a secondary endpoint in patients with pretreated HER2-positive advanced gastric cancer (AGC). Although adverse events caused by T-DXd were generally manageable, approximately 10% of patients experienced treatment-related interstitial lung disease. Based on the results of the DESTINY-Gastric01 trial, T-DXd was approved for HER2-positive pretreated AGC in Japan. This study reviews the preclinical and clinical data of T-DXd for treating HER2-positive gastric cancer.