The drug-antibody conjugate trastuzumab emtansine demonstrated single-agent activity in patients with previously treated HER2-positive disease.

Even with the recent approval of pertuzumab as a component (along with trastuzumab and docetaxel) of a first-line regimen for patients with human epidermal growth factor receptor 2 (HER2)–positive, metastatic breast cancer, the anticipated approval of trastuzumab emtansine (T-DM1) is eagerly awaited by oncologists as a treatment for patients with progressive HER2-positive breast cancer following treatment with trastuzumab. Indeed, clinical experience with T-DM1 — a fusion molecule combining trastuzumab with a cytotoxic (maytansine) utilizing a stable linker (see illustration) — has shown robust clinical activity following prior anti-HER2 therapy with relatively modest toxicity (J Clin Oncol 2011 Feb; 29:398).

Now, investigators have conducted an industry-supported, single-arm, phase II clinical trial to evaluate the effectiveness of T-DM1 (3.6 mg/kg intravenously, every 3 weeks) in 110 patients with metastatic HER-2-positive breast cancer who were previously treated with trastuzumab, lapatinib, an anthracycline, a taxane, and capecitabine. Patients had previously received a median of seven prior nonendocrine agents.

At median follow-up of 17.4 months, the objective response rate (the primary objective) was 34.5%, the clinical benefit rate (inclusive of stable disease) was 48.2%, and median progression-free survival (PFS) was 6.9 months. T-DM1 was well tolerated. Most adverse events were grade 1 or 2. The most common events of any grade were fatigue, nausea, and thrombocytopenia. Grade 3 or 4 thrombocytopenia occurred in 9.1% of patients, and grade 3 fatigue occurred in 4.5%.

Comment: T-DM1 was recently shown to be superior to combination capecitabine and lapatinib in metastatic breast cancer patients who were not as heavily pretreated as those in the current study (JW Oncol Hematol Jul 3 2012). T-DM1 will be rapidly embraced by clinical oncologists once it is approved, and the future development of this agent will likely move to earlier-stage breast cancer and be used in combination with other HER2-targeted agents such as pertuzumab.

Source:Journal Watch Oncology and Hematology