FDA Approves Ado-Trastuzumab Emtansine for HER2-Positive Early Breast Cancer


On May 3, the U.S. Food and Drug Administration (FDA) approved ado-trastuzumab emtansine (T-DM1; Kadcyla) for the adjuvant treatment of patients with HER2-positive early breast cancer who have residual invasive disease after neoadjuvant taxane- and trastuzumab-based treatment.

Patients should be selected based on an FDA-approved companion diagnostic for ado-trastuzumab emtansine. The FDA also approved both the Ventana Medical Systems, Inc, PATHWAY anti-HER-2/neu (4B5) Rabbit Monoclonal Primary Antibody assay and the INFORM HER2 Dual ISH DNA Probe Cocktail assay as companion diagnostic devices for selecting patients.


Approval was based on the KATHERINE trial, a randomized, multicenter, open-label study of 1,486 patients with HER2-positive early breast cancer. Breast tumor samples were required to demonstrate HER2 overexpression defined as 3+ immunohistochemical or in situ hybridization amplification ratio ≥ 2.0, as determined at a central laboratory using one of the companion assays described above. Patients were required to have had neoadjuvant taxane- and trastuzumab-based therapy, with residual invasive tumor in the breast and/or axillary lymph nodes.

Patients received radiotherapy and/or hormonal therapy concurrent with study treatment per local guidelines. They were randomly assigned 1:1 to receive T-DM1 at 3.6 mg/kg intravenously or trastuzumab at 6 mg/kg intravenously on day 1 of a 21-day cycle for 14 cycles.

The trial’s primary endpoint was invasive disease-free survival (IDFS), defined as the time from the date of randomization to first occurrence of ipsilateral invasive breast tumor recurrence; ipsilateral local or regional invasive breast cancer recurrence; distant recurrence; contralateral invasive breast cancer; or death from any cause.

After a median follow-up of 40 months, the trial demonstrated a statistically significant improvement in IDFS in patients who received T-DM1 compared with those who received standard trastuzumab (hazard ratio [HR] = 0.50; 95% confidence interval [CI] = 0.39–0.64; P < .0001). Overall survival data were not mature at the time of the IDFS analysis.

The most common adverse reactions (≥ 25%) with T-DM1 treatment were fatigue, nausea, increased transaminases, musculoskeletal pain, hemorrhage, thrombocytopenia, headache, peripheral neuropathy, and arthralgia.

The recommended T-DM1 dose is 3.6 mg/kg given as an intravenous infusion every 3 weeks (21-day cycle) for a total of 14 cycles for patients with early breast cancer, unless there is disease recurrence or unacceptable toxicity.

View the full prescribing information for ado-trastuzumab emtansine.

The content in this post has not been reviewed by the American Society of Clinical Oncology, Inc. (ASCO®) and does not necessarily reflect the ideas and opinions of ASCO®.