Enhertu

Enhertu, also known as trastuzumab deruxtecan (DS-8201), is an antibody-drug conjugate that targets the HER2 protein on cancer cells. It combines the HER2-directed monoclonal antibody trastuzumab with a topoisomerase I inhibitor, deruxtecan, linked together to deliver the cytotoxic payload directly to cancer cells. After binding to HER2, the conjugate is internalized and the drug is released, causing DNA damage in the target cells and, in some cases, a bystander effect on neighboring tumor cells.

The mechanism of action centers on selective binding to HER2-expressing cells and subsequent intracellular release of the cytotoxic agent. This approach aims to maximize anti-tumor activity while attempting to limit systemic exposure. The bystander effect can contribute to efficacy in tumors with heterogeneous HER2 expression.

Indications for Enhertu include metastatic HER2-positive breast cancer and HER2-expressing gastric or gastroesophageal junction (GEJ) adenocarcinoma. In the United States, the FDA initially approved Enhertu for adults with metastatic HER2-positive breast cancer who have received one or more prior anti-HER2 regimens, with subsequent approvals expanding its use in other settings. It is also approved in several regions for unresectable or metastatic HER2-positive gastric or GEJ cancer after prior systemic therapy. Ongoing studies are exploring use in additional HER2-expressing cancers and earlier lines of therapy.

Safety considerations include common adverse effects such as nausea, fatigue, alopecia, vomiting, anemia, and neutropenia. A notable serious risk is interstitial lung disease or pneumonitis, which can be life-threatening. Other risks include fetal harm, so pregnancy should be avoided. As with many anticancer agents, monitoring for organ function and early recognition of adverse events are important. Developments continue as regulatory agencies assess broader indications and long-term safety data.