DESTINY-Breast06 — Trastuzumab Deruxtecan Versus Physician's Choice Chemotherapy in HR-Positive, HER2-Low or HER2-Ultralow Metastatic Breast Cancer After Endocrine Therapy

Phase 3 · 2024 · Breast Cancer

Design

Randomized open-label to trastuzumab deruxtecan vs physician's choice of single-agent chemotherapy (capecitabine, nab-paclitaxel, or paclitaxel).

Population

HR-positive, HER2-low (IHC 1+ or 2+/ISH-) or HER2-ultralow (IHC 0 with membrane staining) metastatic breast cancer after >=1 line of endocrine-based therapy and no prior chemotherapy for metastatic disease.

Primary Endpoint

progression-free survival (PFS) in the HR+/HER2-low population

Key Result

Median PFS 13.2 vs 8.1 mo in HER2-low (HR 0.62); consistent benefit in the HER2-ultralow subgroup.

Guideline Impact

Supported use of trastuzumab deruxtecan after endocrine therapy in HR+/HER2-low and HER2-ultralow metastatic breast cancer