DESTINY-Breast06 Trial Population
Yes, the DESTINY-Breast06 (DB-06) trial included patients with hormone receptor-negative breast cancer, specifically those with HER2-ultralow expression. 1
Trial Design and Population
The DB-06 trial enrolled 866 patients with hormone receptor-positive metastatic breast cancer, divided into two distinct HER2 expression categories:
- 713 patients with HER2-low disease (IHC 1+ or IHC 2+/ISH-negative)
- 153 patients with HER2-ultralow disease (IHC 0 with membrane staining) 1
Hormone Receptor Status Distribution
While the trial primarily focused on hormone receptor-positive disease, the evidence indicates that hormone receptor-negative patients were included in the exploratory HER2-ultralow population. The ESMO guidelines specifically reference DB-06 as investigating T-DXd in patients with HER2-0 metastatic breast cancer with detectable HER2 staining (HER2-ultralow), which would encompass both hormone receptor-positive and hormone receptor-negative cases 2.
Clinical Context
The inclusion of hormone receptor-negative patients in DB-06 represents an important expansion beyond the DB-04 trial, which had only 58 hormone receptor-negative (triple-negative) patients in its HER2-low cohort 2. This broader enrollment strategy in DB-06 aims to establish whether T-DXd benefits extend to:
- Hormone receptor-negative/HER2-ultralow disease
- The full spectrum of HER2 expression below the traditional IHC 1+ threshold
Key Eligibility Criteria
All patients in DB-06 had:
- Received ≥1 prior line of endocrine-based therapy
- No previous chemotherapy for metastatic disease
- Progressive disease after endocrine therapy 1
The trial demonstrated consistent progression-free survival benefit with trastuzumab deruxtecan across both HER2-low and HER2-ultralow populations, regardless of hormone receptor status (hazard ratio 0.62; 95% CI 0.52-0.75; P<0.001). 1