Multinational phase 3 trial of trastuzumab deruxtecan after endocrine therapy for metastatic breast cancer

Outcomes in patients with HR-positive metastatic breast cancer (mBC) worsen after one or more lines of endocrine-based therapy. The multinational phase 3 Destiny-Breast06 trial compared trastuzumab deruxtecan (T-DXd) versus investigator’s choice or chemotherapy (ICC) for HR-positive, HER2-low or HER2-ultralow mBC after one or more lines of endocrine-based therapy. The primary endpoint was progression-free survival (according to blinded independent central review) among patients with HER2-low disease. The median progression-free survival among HER2-low patients was 13.2 months in the T-DXd group and 8.1 months in the ICC group (HR 0.62; p<0.001); the results were consistent in the exploratory HER2-ultralow populations. Data for overall survival were immature. Adverse events of grade 3 or higher occurred in 52.8% of the patients in the T-DXd group and 44.4% of the patients in the ICC group. The authors conclude that among patients with HR-positive, HER2- low or HER2-ultralow mBC who had received one or more lines of endocrine-based therapy, treatment with T-DXd resulted in longer progression-free survival than ICC. No new safety signals were identified.