Trastuzumab emtansine in breast cancer

Trastuzumab emtansine (T-DM1) is a human epidermal growth factor receptor 2 (HER2)-targeted antibody-drug conjugate (ADC) composed of trastuzumab, a stable linker (MCC), and the cytotoxic agent DM1 (derivative of maytansine). Administration of T-DM1 leads to limited systemic exposure of free DM1, with no evidence of DM1 accumulation after repeated dosing.

Phase I and Phase II clinical trials with T-DM1 as a single agent and in combination with paclitaxel, docetaxel, and pertuzumab have shown substantial clinical activity and a favorable safety profile. A randomized, open-label, first-line trial comparing trastuzumab and docetaxel with single agent T-DM1 showed a significant improved progression-free survival for T-DM1.

T-DM1 has successfully completed second-line Phase III development for advanced HER2-positive breast cancer. The Phase III EMILIA study demonstrated an overall survival benefit for T-DM1 compared to the combination of lapatinib and capecitabine in taxane-trastuzumab pretreated patients. T-DM1 may offer delivery on a personalized basis of very potent cytotoxic agents in a cellular selective manner.