Ado-trastuzumab emtansine for the treatment of human epidermal growth factor receptor 2–positive metastatic breast cancer

PURPOSEAn update on completed and ongoing clinical trials of ado-trastuzumab emtansine for the treatment of metastatic breast cancer (MBC) is presented. SUMMARYAdo-trastuzumab emtansine (Kadcyla, Genentech), the first U.S.-approved antibody–drug conjugate for MBC, is indicated for use as a single-agent therapy in patients with human epidermal growth factor receptor 2 (HER2)–positive MBC who have received prior treatment with unconjugated trastuzumab and a taxane-based regimen. The standard dosage of ado-trastuzumab is 3.6 mg/kg i.v. every three weeks. In completed Phase II or III clinical trials, ado-trastuzumab was found to confer significant survival and quality-of-life benefits. The largest of those trials (the EMILIA study, n = 991) showed that ado-trastuzumab was superior to a regimen of lapatinib plus capecitabine in terms of progression-free survival (9.6 months versus 6.4 months, p < 0.001) and overall survival (30.9 months versus 25.1 months, p < 0.001); it also had a more favorable tolerability profile, with lower rates of treatment-limiting adverse effects. The most common adverse effects of ado-trastuzumab are thrombocytopenia (reported in about 12% of clinical trial participants overall) and increased transaminase levels. Two ongoing Phase III trials—the TH3RESA study (slated for completion in June 2015) and the MARIANNE study (estimated completion in 2016)—may help determine the optimal role of ado-trastuzumab relative to other HER2-targeted agents and its potential use as a front-line therapy for both heavily pretreated and treatment-naive patients with MBC. CONCLUSIONWith a novel targeted mechanism of action, ado-trastuzumab is an effective treatment option for HER2-positive MBC in previously treated patient populations.