Five-year follow-up of DESTINY-Breast03: T-DXd vs T-DM1 in HER2+ MBC

In this video, Dr Andrea Gombos discusses the final 5-year follow-up results of the phase III DESTINY-Breast03 trial, which compared trastuzumab deruxtecan (T-DXd) with trastuzumab emtansine (T-DM1) in patients with HER2-positive metastatic breast cancer previously treated with trastuzumab and a taxane. 

The trial included 524 patients, randomised 1:1 to T-DXd or T-DM1. At the time of the analysis, only a small number of patients remained on treatment, with most discontinuations occurring due to disease progression. Treatment discontinuation due to toxicity was reported more frequently with T-DXd than with T-DM1 (26.8% vs 10.0%). 

A long-term efficacy benefit was observed with T-DXd, including a significantly improved progression-free survival (PFS) and a sustained improvement in overall survival (OS) compared with T-DM1, confirming T-DXd as a highly effective second-line option in this setting. 

Regarding safety, no new safety signals were reported with longer follow-up. Interstitial lung disease (ILD) was reported in 17.5% of patients treated with T-DXd, but events were manageable and no fatal cases were reported in this update. 

Overall, this 5-year follow-up reinforces the role of T-DXd as the preferred standard of care after progression on first-line HER2-directed therapy in metastatic breast cancer.