Trastuzumab emtansine (Kadcyla®), an antibody–drug conjugate of trastuzumab (Herceptin®) connected by a thioether linker to the microtubule inhibitor DM1 (a cytotoxic derivative of maytansine), provides direct intracellular delivery of the… Click to show full abstract
Trastuzumab emtansine (Kadcyla®), an antibody–drug conjugate of trastuzumab (Herceptin®) connected by a thioether linker to the microtubule inhibitor DM1 (a cytotoxic derivative of maytansine), provides direct intracellular delivery of the potent cytotoxin DM1 to HER2-overexpressing cells, while retaining trastuzumab activity. Its approval in metastatic/advanced breast cancer (BC) has been extended to include single-agent adjuvant treatment of HER2-positive early BC in patients with residual invasive disease in the breast and/or lymph nodes after neoadjuvant taxane-based and HER2-targeted treatment. In the pivotal KATHERINE trial in this population, significantly more trastuzumab emtansine than trastuzumab recipients were estimated to be free of invasive disease recurrence at 3 years, with a 50% reduction in the risk of invasive disease recurrence or death. The tolerability of trastuzumab emtansine in early BC was consistent with its known safety profile; as expected, adverse events were more common with trastuzumab emtansine than with trastuzumab. Recently updated international and national treatment guidelines recommend trastuzumab emtansine as a preferred option in this high-risk BC population.
               
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