On May 3, 2019, the FDA approved a new indication for ado-trastuzumab emtansine (Kadcyla; Genentech) for the adjuvant treatment of patients with HER2-positive early breast cancer who have residual invasive disease after neoadjuvant taxane- and trastuzumab (Herceptin)-based treatment. The FDA granted this application priority review. Ado-trastuzumab emtansine was granted breakthrough therapy designation for the adjuvant treatment of patients with HER2-positive early breast cancer who have residual disease after preoperative systemic treatment. Ado-trastuzumab emtansine was initially approved in 2013 for the treatment of metastatic HER2-positive breast cancer.
The FDA also approved the Ventana Medical Systems PATHWAY anti-HER-2/neu Rabbit Monoclonal Primary Antibody assay and the INFORM HER2 Dual ISH DNA Probe Cocktail assay for selecting patients for this adjuvant treatment based on these companion diagnostic assays.
This new indication was based on a randomized, multicenter, open-label trial of 1486 patients with HER2-positive early breast cancer. Tumor samples were used to demonstrate HER2 overexpression using the Ventana’s PATHWAY assays. Patients had to have had neoadjuvant taxane- and trastuzumab-based therapy with residual invasive tumor in the breast and/or the axillary lymph nodes. Patients received radiotherapy and/or hormonal therapy with the study treatment based on relevant guidelines. The patients were randomized in a 1:1 ratio to ado-trastuzumab emtansine 3.6 mg/kg or to trastuzumab 6 mg/kg on day 1 of each 21-day cycle, for a total of 14 cycles.
The primary end point was invasive disease-free survival, defined as the time from the date of randomization to first 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, significant improvement was seen in invasive disease-free survival in patients who received ado-trastuzumab emtansine compared with those who received trastuzumab (hazard ratio, 0.50; P <.0001). At the time of the data analysis, the overall survival data were not mature.
The most common (≥25%) adverse events with ado-trastuzumab emtansine were fatigue, nausea, increased transaminases, musculoskeletal pain, hemorrhage, thrombocytopenia, headache, peripheral neuropathy, and arthralgia.