Trastuzumab emtansine (T-DM1) is an antibody-drug conjugate comprising trastuzumab (Herceptin) linked to the chemotherapy agent emtansine (DM1). It specifically targets HER2-positive cancers, not only inhibiting HER2 signalling but also releasing emtansine directly into the tumour cells (a so-called 'smart bomb' approach), thus sparing healthy cells the drug’s cytotoxic effects.
Investigators presented the results of the first phase III study of trastuzumab emtansine at the 48th annual meeting of the American Society of Clinical Oncology (ASCO) earlier this month.
The EMILIA study enrolled 991 people with HER2-positive metastatic breast cancer that had progressed despite treatment with trastuzumab and a taxane. Patients were randomised to receive trastuzumab emtansine 3.6mg/kg every 3 weeks, or lapatinib 1.25g daily plus capecitabine 2g/m2 (on days 1–14) every 3 weeks until disease progression or unmanageable toxicity occurred.
Follow-up continued for a median of 12.9 months in the trastuzumab emtansine group and 12.4 months in the lapatinib plus capecitabine group.
The researchers found that patients who received the antibody-drug conjugate lived significantly longer without disease progression than those who received lapatinib plus capecitabine (median 9.6 months vs 6.4 months, p<0.0001). Trastuzumab emtansine was associated with a lower incidence of serious adverse events than lapatinib/capecitabine (40.8% vs 57%).
Data on overall survival are due to be released at a later date.
Two other phase III studies of trastuzumab emtansine are underway. MARIANNE is comparing the antibody-drug conjugate with two different dual therapy regimens in patients who have not yet received treatment for their metastatic disease. TH3RESA is comparing trastuzumab emtansine to the physician’s choice of treatment in patients who have already received trastuzumab and lapatinib.
The developer of trastuzumab emtansine, Roche, plans to submit the drug for regulatory approval this year.