Trastuzumab emtansine (T-DM1): Een antilichaamgeneesmiddelconjugaat voor gerichte behandeling van HER2-positieve gemetastaseerde borstkanker

Approximately 25% of patients with metastatic breast cancer (MBC) have overexpression of HER2 receptors on their tumour. This has led to the development of several drugs targeting the HER2 receptor. Unfortunately, ultimately resistance to these agents develops, leading to tumour progression. Recently, trastuzumab emtansine (T-DM1), an antibody-drug conjugate, has been developed. In T-DM1 the HER2 targeting antibody trastuzumab (T) is covalently bound to the cytotoxic agent mertansine (DM1) with a thioether linker. DM1 is released in tumour cells after internalisation of T-DM1 and subsequent proteolytic degradation, resulting in a tumour-specific effect. Various clinical trials have been performed in which T-DM1 was tested in MBC patients after failure of a HER2 targeting regimen. A three-weekly schedule of T-DM1 (3.6 mg/kg) proved to be safe and well tolerable, with nausea, fatigue and thrombocytopenia (dose-limiting) as most commonly reported side effects. In the pivotal phase III trial an objective response rate of 43.6% was observed in MBC patients; furthermore, progression-free and overall survival (9.6 and 30.9 months, respectively) were significantly longer in the T-DM1 group than in the control group (lapatinib + capecitabine; 6.4 and 25.1 months, respectively). These results show that T-DM1 is a promising new treatment option in MBC. Prescribers and pharmacists should be aware of potential medication errors caused by name confusion between trastuzumab emtansine and trastuzumab.