Ado-Trastuzumab Emtansine Granted FDA Approval in HER2-Positive Early Breast Cancer
Posted: Tuesday, May 7, 2019
On May 3, 2019, the U.S. Food and Drug Administration (FDA) approved ado-trastuzumab emtansine (also known as 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 for this treatment based on an FDA-approved companion diagnostic for ado-trastuzumab emtansine.
Approval was based on results from the KATHERINE trial (ClinicalTrials.gov identifier NCT01772472), a randomized, multicenter, open-label study of 1,486 patients with HER2-positive early breast cancer. 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. Patients were randomly assigned to receive ado-trastuzumab emtansine intravenously or trastuzumab intravenously.
The trial’s primary endpoint was invasive disease–free survival, defined as the time from the date of randomization to the 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 invasive disease–free survival in patients who received ado-trastuzumab emtansine compared with those who received trastuzumab (hazard ratio = 0.50). Overall survival were not mature at the time of the analysis of invasive disease–free survival.
The most common adverse reactions (≥ 25%) with ado-trastuzumab emtansine were fatigue, nausea, increased transaminases, musculoskeletal pain, hemorrhage, thrombocytopenia, headache, peripheral neuropathy, and arthralgia.
The recommended dose of ado-trastuzumab emtansine is 3.6 mg/kg given as an intravenous infusion every 3 weeks for a total of 14 cycles for patients with early breast cancer, unless there is disease recurrence or unacceptable toxicity.