Trastuzumab Deruxtecan Proves Effective in DESTINY-Breast06 Trial for HER2-low or HER2-ultralow Metastatic Breast Cancer

The DESTINY-Breast06 trial is a Phase III clinical study comparing the efficacy and safety of trastuzumab deruxtecan (T-DXd) in patients with hormone receptor-positive (HR+), HER2-low or HER2-ultralow metastatic breast cancer (MBC). The trial enrolled 866 patients who were HR+ with HER2-low (IHC 1+ or 2+/ISH-) or HER2-ultralow (IHC 0 with faint incomplete membrane staining in ≤10% of tumor cells). Patients were randomized to receive either T-DXd or physician's choice.

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Results showed that T-DXd provided a clinically meaningful benefit in PFS compared to CT(Chemotherapy). In the HER2-low population, median PFS was 13.2 months for T-DXd versus 8.1 months for CT (hazard ratio [HR]: 0.62; 95% CI: 0.51-0.74; P <.0001). In the ITT population, median PFS was also 13.2 months for T-DXd compared to 8.1 months for CT (HR: 0.63; 95% CI: 0.53-0.75; P <.0001). Patients with HER2-ultralow disease similarly benefited, with median PFS of 13.2 months for T-DXd versus 8.3 months for CT (HR: 0.78; 95% CI: 0.50-1.21).

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In conclusion, the DESTINY-Breast06 trial demonstrated that T-DXd is an effective treatment option for patients with HR+/HER2-low or ultralow MBC who have progressed on prior endocrine therapy, providing a significant PFS benefit over standard chemotherapy without new safety concerns

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Reference: Giuseppe Curigliano et al., Trastuzumab deruxtecan (T-DXd) vs physician’s choice of chemotherapy (TPC) in patients (pts) with hormone receptor-positive (HR+), human epidermal growth factor receptor 2 (HER2)-low or HER2-ultralow metastatic breast cancer (mBC) with prior endocrine therapy (ET): Primary results from DESTINY-Breast06 (DB-06). JCO 42, LBA1000-LBA1000(2024).

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