Multinational phase 3 trial of trastuzumab deruxtecan plus pertuzumab for HER2-positive metastatic breast cancer

The multinational phase 3 DESTINY-Breast09 trial randomized patients with HER2-positive metastatic breast cancer and no previous chemotherapy or HER2-directed therapy for metastatic disease 1:1:1 to receive trastuzumab deruxtecan T-DXd) plus pertuzumab, T-DXd plus placebo, or a taxane, trastuzumab, and pertuzumab (THP). The primary endpoint was progression-free survival as assessed by blinded independent central review. Interim analysis of T-DXd plus pertuzumab versus THP has now been reported. The median progression-free survival was 40.7 months with T-Dxd plus pertuzumab (383 patients) and 26.9 months with THP (387 patients) (HR 0.56; p<0.00001); the incidence of a confirmed response was 85.1% and 78.6%, respectively, with complete responses in 15.1% and 8.5%, with a median duration of response of 39.2 months and 26.4 months. The incidence of grade 3 of higher adverse events was 63.5% with T-DXd plus pertuzumab and 62.3% with THP. The authors conclude that T-DXd plus pertuzumab led to a significantly lower risk of progression or death than THP when used as first-line treatment for HER2-positive metastatic breast cancer.