History
In 2013, trastuzumab emtansine was approved in the United States for the treatment of adults with HER2-positive, metastatic breast cancer who previously received trastuzumab and a taxane, separately or in combination.[12][20]
Referred to as T-DM1 during clinical research, trastuzumab emtansine was reviewed under the FDA's priority review program.[12]
The safety and effectiveness of trastuzumab emtansine were evaluated in a clinical study of 991 patients randomly assigned to receive trastuzumab emtansine or lapatinib plus capecitabine, another chemotherapy drug.[12] Patients received treatment until either the cancer progressed or the side effects became intolerable.[12] The study was designed to measure progression-free survival, the length of time patients lived without the cancer progressing, and overall survival, the length of time patients lived before death.[12]
Results showed that patients treated with trastuzumab emtansine had a median progression-free survival of 9.6 months compared to 6.4 months in patients treated with lapatinib plus capecitabine.[12] The median overall survival was 30.9 months in the trastuzumab emtansine group and 25.1 months in the lapatinib plus capecitabine group.[12]
The U.S. Food and Drug Administration (FDA) approved trastuzumab emtansine in February 2013, and granted the application for Kadcyla to Genentech.[12] The FDA granted the application for trastuzumab emtansine priority review and breakthrough therapy designations.
In 2013, trastuzumab emtansine was approved in the UK,[21] and the EU.[22]
In 2019, trastuzumab emtansine was approved in the United States for the adjuvant treatment of patients with HER2-positive early breast cancer (EBC) who have residual invasive disease after neoadjuvant taxane and trastuzumab-based treatment.[23]
Approval was based on KATHERINE (NCT01772472[24]), a randomized, multicenter, open-label trial of 1486 patients with HER2-positive EBC.[23] Breast tumor samples were required to demonstrate HER2 overexpression defined as 3+ IHC or ISH amplification ratio ≥ 2.0 determined at a central laboratory using Ventana's PATHWAY anti-HER2-/neu (4B5) Rabbit Monoclonal Primary Antibody or INFORM HER2 Dual ISH DNA Probe Cocktail assays.[23] Patients were required to have had neoadjuvant taxane and trastuzumab-based therapy with residual invasive tumor in the breast and/or axillary lymph nodes.[23] Patients received radiotherapy and/or hormonal therapy concurrent with study treatment per local guidelines.[23] Patients were randomized (1:1) to receive trastuzumab emtansine 3.6 mg/kg intravenously or trastuzumab 6 mg/kg intravenously on day 1 of a 21-day cycle for 14 cycles.[23]
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.[23] After a median follow-up of 40 months, the trial demonstrated a statistically significant improvement in IDFS in patients who received trastuzumab emtansine compared with those who received trastuzumab (HR 0.50; 95% CI: 0.39, 0.64; p<0.0001).[23] Overall survival data were not mature at the time of the IDFS analysis.[23]
