Updated efficacy and safety analyses of DESTINY-Breast03 trial, recently published on Nature Medicine, confirm a superior efficacy for trastuzumab-deruxtecan (T-DXd) over trastuzumab-emtansine (T-DM1) in patients with advanced HER2+ metastatic breast cancer previously treated with taxane and trastuzumab.

In DESTINY-Breast03 trial, 524 HER2+ metastatic breast cancer patients previously treated with taxane and trastuzumab were randomized to T-DXd or T-DM1; at a median follow-up of 28 months, T-DXd demonstrated significantly improved efficacy over T-DM1. These new data from a median follow-up of 41 months include secondary and exploratory efficacy endpoints as well as an update analysis of primary endpoints. Median progression-free survival was 29 versus 7.2 months, the 36-month progression-free survival rate was 45.7% versus 12.4% and median overall survival was 52.6 versus 42.7 months with T-DXd versus T-DM1, respectively; treatment-emergent adverse events were consistent with the previous analyses. As authors conclude, «This long-term analysis reinforces the superiority of T-DXd over T-DM1 in patients with metastatic breast cancer previously treated with taxane and trastuzumab, with the longest median overall survival reported in this disease setting and more than two-thirds (67.6%) of patients still alive at 3 years. The safety profile of T-DXd continues to be manageable with no cumulative toxicities observed with longer follow-up. Analyses on the impact of T-DXd on long-term responders across studies and exploring the efficacy of T-DXd in the earlier metastatic breast cancer setting (DESTINY-Breast09) are ongoing».