Datopotamab deruxtecan: rational strategies, novel advancements, challenges, and future perspectives

Antibody-drug conjugates have recently revolutionized the treatment scenario of several tumors, including breast cancer. Among these, Datopotamab deruxtecan (Dato-DXd) is an ADC composed of a humanized anti-TROP2 monoclonal antibody linked to a potent exatecan-derived topoisomerase I inhibitor payload, deruxtecan (DXd), via a plasma-stable, selectively cleavable linker. Dato-DXd has shown notable efficacy and an overall tolerable safety profile, according to available evidence. Herein, we provide an overview of the pharmacological features, mechanisms of action, clinical efficacy, and adverse events of Dato-DXd in breast cancer. Furthermore, the current review proposes strategies to optimize patient management and accelerate the clinical development of Dato-DXd in this setting.