Trastuzumab Deruxtecan for HER2+ Advanced Breast Cancer

Trastuzumab deruxtecan (T-DXd, DS-8201), an anti-HER2 antibody-drug conjugate, has shown significant clinical benefits in HER2+ metastatic breast cancer patients. In the phase 2 DESTINY-Breast01 trial, T-DXd demonstrated an objective response of 60.9% and median progression-free survival of 16.4 months, laying the foundation for accelerated approval in HER2+ metastatic breast cancer patients who have received two or more prior anti-HER2-based regimens in the metastatic setting. Moreover, T-DXd exhibited promising antitumor efficacy against HER2-low-expressing metastatic breast cancer. Its distinctive side effect was pneumonitis, with a 13.6% incidence. It is approved in the US with boxed warnings for interstitial lung disease and embryo-fetal toxicity. This review focuses on preclinical, pharmacokinetic and pharmacodynamic data on T-DXd and clinical evidence of its antitumor activity (both as monotherapy and in combination) and tolerability in metastatic breast cancer.