TDM1

T-DM1, also known as trastuzumab emtansine, is an antibody-drug conjugate used in the treatment of certain HER2-positive cancers. It combines the monoclonal antibody trastuzumab with the cytotoxic agent DM1 (a maytansine derivative) linked by a stable non-cleavable thioether linker. The design aims to deliver the cytotoxic payload specifically to HER2-overexpressing tumor cells.

Mechanism of action involves dual activity. The trastuzumab component targets and binds to HER2 on cancer cells, facilitating internalization of the conjugate. Inside the cell, the antibody is degraded in lysosomes, releasing DM1 which disrupts microtubule dynamics and induces cell death. The trastuzumab portion can also contribute to anti-tumor effects through inhibition of HER2 signaling and, to some extent, antibody-dependent cellular cytotoxicity.

Clinical use and indications include treatment of adults with HER2-positive metastatic breast cancer who have previously received trastuzumab and a taxane. Kadcyla is the marketed product name for T-DM1. The drug is studied in other HER2-positive cancers and different settings, including adjuvant therapy in selected high-risk situations, with guidelines guiding its use in specific contexts.

Safety considerations emphasize monitoring for hematologic and hepatic toxicity, fatigue, and nausea. Cardiac toxicity is a known risk with HER2-directed therapies, so periodic evaluation of left ventricular function is recommended during treatment. T-DM1 is administered intravenously, typically every three weeks, with dosing decisions based on response and tolerability.