Post-Trastuzumab Deruxtecan Treatments Show Promise in HER2+ Breast Cancer

This nationwide Japanese study addresses a critical gap in cancer treatment: what works best after patients stop trastuzumab deruxtecan (T-DXd), a breakthrough antibody-drug conjugate for HER2-positive metastatic breast cancer. With T-DXd now standard second-line therapy, understanding optimal follow-up treatments is essential for patient care.

Researchers analyzed 664 patients from 222 medical centers who discontinued T-DXd between May 2020 and November 2021 and started subsequent treatments. The majority (73.2%) received continued HER2-targeted therapy, split between anti-HER2 antibodies (54.4%) and HER2 tyrosine kinase inhibitors (17.0%). The remaining patients received chemotherapy, hormone therapy, or other treatments.

Overall outcomes were encouraging: median progression-free survival reached 4.1 months and overall survival 16.2 months from starting post-T-DXd treatment. Notably, patients who discontinued T-DXd due to adverse events rather than disease progression, and those who had complete or partial responses to T-DXd, showed numerically longer survival times. Anti-HER2 antibodies and HER2-TKIs performed similarly in effectiveness.

A key safety finding was the low 3.2% rate of interstitial lung disease (ILD) recurrence during subsequent treatment. ILD is T-DXd's most serious side effect, causing treatment discontinuation in 5-15% of patients. The low recurrence rate suggests subsequent HER2-targeted therapies are relatively safe even for patients who developed this complication.

These real-world results support continuing HER2-targeted therapy after T-DXd discontinuation, particularly for patients who responded well initially or stopped due to side effects rather than treatment failure.