von Minckwitz G, et al. - Researchers investigated the invasive disease-free survival (defined as freedom from ipsilateral invasive breast tumor recurrence, ipsilateral locoregional invasive breast cancer recurrence, contralateral invasive breast cancer, distant recurrence, or death from any cause) when trastuzumab emtansine (T-DM1), an antibody–drug conjugate of trastuzumab and the cytotoxic agent emtansine (DM1), a maytansine derivative and microtubule inhibitor, was administered to patients with metastatic breast cancer that were previously treated with chemotherapy plus human epidermal growth factor receptor 2 (HER2)-targeted therapy. In these patients, T-DM1 administration led a reduction in the risk of recurrence of invasive breast cancer or death by 50% than administering trastuzumab alone.

Methods

• In this phase 3, open-label trial, researchers included patients with HER2-positive early breast cancer who were found to have residual invasive disease in the breast or axilla at surgery after receiving neoadjuvant therapy containing a taxane (with or without anthracycline) and trastuzumab.
• Adjuvant T-DM1 or trastuzumab for 14 cycles was administered to the patients randomly.
• Invasive disease–free survival (defined as freedom from ipsilateral invasive breast tumor recurrence, ipsilateral locoregional invasive breast cancer recurrence, contralateral invasive breast cancer, distant recurrence, or death from any cause) was assessed as the primary end point.

Results

• Researchers randomly assigned 1486 patients (743 in the T-DM1 group and 743 in the trastuzumab group); in the interim analysis, 91 patients in the T-DM1 group (12.2%) and 165 patients in the trastuzumab group (22.2%) reported invasive disease or death.
• The estimated percentage of patients who were free of invasive disease at 3 years was 88.3% and 77.0% in T-DM1 group and trastuzumab group, respectively.
• Significantly higher invasive disease–free survival was observed in the T-DM1 group than that observed in the trastuzumab group (hazard ratio for invasive disease or death, 0.50; 95% confidence interval, 0.39 to 0.64; P<0.001).
• Distant recurrence as the first invasive-disease event occurred in 10.5% and 15.9% of patients in T-DM1 group and trastuzumab group, respectively.
• The safety data were consistent with the known safety profile of T-DM1; more adverse events were associated with T-DM1 than with trastuzumab alone.