Trastuzumab emtansine is an antibody-drug conjugate comprising trastuzumab, a humanised IgG1 monoclonal antibody with HER2-targeted antitumour properties, covalently linked to DM1, a microtubule inhibitor.1
This drug-antibody conjugate confers selectivity of the cytotoxic agent for HER2-overexpressing malignant cells, resulting in receptor-mediated internalisation and subsequent degradation of the conjugate to DM1-containing cytotoxic catabolites.1,2
Efficacy and safety of trastuzumab emtansine were assessed in the open-label phase III EMILIA study which included 991 patients with HER2-positive unresectable locally advanced or metastatic breast cancer, who had received prior treatment with trastuzumab and a taxane.2
Patients were randomly assigned to trastuzumab emtansine (3.6mg/kg intravenously, n=495) every 21 days or oral lapatanib (1.25g daily) plus oral capecitabine (1g/m2 every 12 hours) on days one to 14 of each 21-day treatment cycle (n=496).2
Tumour assessments were performed at baseline and every six weeks thereafter until investigator-assessed disease progression, with an additional assessment six weeks after progression.2
Patients in the trastuzumab emtansine group had significantly improved progression-free survival (as assessed by independent review) compared with those in the lapatinib/capecitabine group (median survival, 9.6 months versus 6.4 months, respectively [stratified hazard ratio for progression or death from any cause, 0.65; 95% CI 0.55–0.77, p<0.001]).2
In addition, median overall survival at the second of two interim analyses was significantly greater in the trastuzumab emtansine group than in the lapatinib/capecitabine group, crossing the stopping boundary for efficacy (30.9 months versus 25.1 months [hazard ratio for death from any cause, 0.68; CI 95% 0.55–0.85, p<0.001]).2
Trastuzumab emtansine was also shown to be superior to lapatinib/capecitabine in terms of the secondary endpoints, including investigator-assessed progression-free survival, objective response rate and median duration of response.2
In the safety population (n=978), the incidence of adverse events of grade 3 or above was greater in the lapatinib/capecitabine group than in the trastuzumab emtansine group (57% versus 40.8%).2
The most commonly reported grade 3 or 4 adverse events in the trastuzumab emtansine group were thrombocytopenia (12.9%) and elevated AST (4.3%) and AST (2.9%) compared with diarrhoea (20.7%) and hand-foot syndrome (16.4%) in the lapatinib/capecitabine group.2
- Kadcyla Summary of Product Characteristics, November 2013.
- Verma S et al. N Engl J Med 2012; 367: 1783–91.
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Further information: Roche