Multinational phase 3 trial of postneoadjuvant trastuzumab deruxtecan versus trastuzumab emtansine for HER2-positive early breast cancer

Patients with HER2-positive early breast cancer and residual disease after neoadjuvant therapy are at high risk for recurrence. The multinational phase 3 DESTINY-Breast05 trial investigated postneoadjuvant trastuzumab deruxtecan (T-DXd) as compared with the current standard treatment trastuzumab emtansine (T-DM1) in patients with HER2-positive breast cancer with residual invasive disease and node-positive disease at surgery or inoperable disease at diagnosis. The primary end point was invasive disease-free survival, and the key secondary end point was disease-free survival. The T-DXd group consisted of 818 patients and the T-DM1 group consisted of 817 patients. The median duration of follow-up was approximately 30 months in each group. For both invasive disease-free survival and disease-free survival, T-DXd was superior to T-DM1, The most common adverse events were nausea, constipation, decreased neutrophil count, and vomiting with T-DXd and increased liver-enzyme levels and decreased platelet count with T-DM1. The incidence of adjudicated drug-related interstitial lung disease (ILD) was higher with T-DXd than with T-DM1 (9.6% versus 1.6%); two patients with ILD in the T-DXd group died. The authors conclude that in patients with high-risk, residual invasive HER2-positive breast cancer, postneoadjuvant T-DXd resulted in higher likelihood of invasive disease-free survival than T-DM1. The risk of ILD requires appropriate monitoring and management.