Kadcyla: a new option in locally advanced or metastatic breast cancer

2 January 2014

Kadcyla (trastuzumab emtansine) is indicated in HER2-positive, unresectable locally advanced or metastatic breast cancer in patients previously treated with trastuzumab and a taxane, who have either received prior therapy for locally advanced or metastatic disease or developed disease recurrence during or within six months of completing adjuvant therapy.

Kadcyla is administered as an intravenous infusion every 21 days until disease progression or unacceptable toxicity.

PHARMACOLOGY

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

CLINICAL STUDIES

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

Survival benefit

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

Safety profile

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

References: