DESTINY-Breast06
Trial question
What is the role of trastuzumab deruxtecan in patients with HR+ metastatic breast cancer who had received endocrine-based therapy?
Study design
Multi-center
Open label
RCT
Population
866 patients (865 female, 1 male).
Inclusion criteria: patients with HR+ metastatic breast cancer with low or ultra-low expression of HER2 who had received one or more lines of endocrine-based therapy.
Key exclusion criteria: lung-specific intercurrent clinically significant disease; uncontrolled or significant CVD or infection; spinal cord compression or clinically active CNS metastases.
Interventions
N=436 trastuzumab deruxtecan (intravenous administration of 5.4 mg/kg every 3 weeks).
N=430 chemotherapy (physician's choice of single-agent chemotherapy, such as capecitabine, nab-paclitaxel, or paclitaxel).
Primary outcome
Median progression-free survival patients with human epidermal growth factor receptor 2-low disease
13.2 months
8.1 months
13.2 months
9.9 months
6.6 months
3.3 months
0.0 months
Trastuzumab
deruxtecan
Chemotherapy
Significant
increase ▲
Significant increase in median progression-free survival patients with HER2-low disease (13.2 months vs. 8.1 months; HR 1.61, 95% CI 1.33 to 1.92).
Secondary outcomes
Significant increase in median progression-free survival in the intention-to-treat population (13.2 months vs. 8.1 months; HR 1.56, 95% CI 1.32 to 1.85).
No significant difference in overall survival at 12 months in patients with HER2-low disease (87.6% vs. 81.7%; HR 1.21, 95% CI 0.95 to 1.51).
Safety outcomes
No significant difference in adverse events.
Conclusion
In patients with HR+ metastatic breast cancer with low or ultra-low expression of HER2 who had received one or more lines of endocrine-based therapy, trastuzumab deruxtecan was superior to chemotherapy with respect to median progression-free survival patients with HER2-low disease.
Reference
Aditya Bardia, Xichun Hu, Rebecca Dent et al. Trastuzumab Deruxtecan after Endocrine Therapy in Metastatic Breast Cancer. N Engl J Med. 2024 Dec 5;391(22):2110-2122.
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