Patritumab deruxtecan in breast cancer: clinical evidence and perspectives on an emerging HER3-targeted therapy

Patritumab deruxtecan, a new-generation antibody-drug conjugate targeting human epidermal growth factor receptor 3 (HER3), demonstrates therapeutic potential in breast cancer (BC). It combines a humanized anti-HER3 monoclonal antibody with a potent topoisomerase I inhibitor, deruxtecan (DXd), via a cleavable linker. Patritumab deruxtecan enables targeted delivery of cytotoxic agents to HER3-expressing tumor cells, inducing DNA damage and apoptosis while exhibiting a potent bystander effect. This review summarizes the latest clinical trial data and basic research findings to discuss the efficacy and safety of patritumab deruxtecan in BC treatment. Preclinical investigations have confirmed its efficacy across diverse BC subtypes, including HER2-positive (HER2+), hormone receptor-positive (HR+)/HER2-negative (HER2−), and triple-negative models, regardless of baseline HER3 expression levels. Clinical evidence further supports its antitumor activity in both early and advanced disease settings, even in heavily pretreated populations and those with central nervous system(CNS) disease. The safety profile is characterized primarily by hematologic and gastrointestinal adverse events, with a relatively low incidence of interstitial lung disease. The review also provides an in-depth analysis of its mechanism of action, early- and late-phase clinical results, and potential applications in neoadjuvant, advanced, and metastatic contexts, including HER2+, HR+/HER2−, triple-negative, and HER3-mutant BCs, as well as brain metastases and leptomeningeal disease(LMD). Additionally, it examines the potential role of patritumab deruxtecan in overcoming treatment resistance and disease recurrence.