DESTINY-Breast03
Trial question
What is the role of trastuzumab deruxtecan in patients with advanced HER2+ metastatic breast cancer?
Study design
Multi-center
Open label
RCT
Population
524 patients (522 female, 2 male).
Inclusion criteria: patients with advanced HER2+ metastatic breast cancer previously treated with taxane and trastuzumab.
Key exclusion criteria: previous treatment with an anti-HER2 antibody drug conjugate in the metastatic setting; uncontrolled or significant CVD; ILD/pneumonitis; spinal cord compression or clinically active CNS metastases.
Interventions
N=261 trastuzumab deruxtecan (intravenous dose of 5.4 mg/kg every 3 weeks).
N=263 trastuzumab emtansine (intravenous dose of 3.6 mg/kg every 3 weeks).
Primary outcome
Median progression-free survival
29 months
7.2 months
29.0 months
21.8 months
14.5 months
7.3 months
0.0 months
Trastuzumab
deruxtecan
Trastuzumab
emtansine
Significant
increase ▲
Significant increase in median progression-free survival (29 months vs. 7.2 months; HR 3.33, 95% CI 2.63 to 4.17).
Secondary outcomes
Significant increase in median overall survival (52.6 months vs. 42.7 months; HR 1.37, 95% CI 1.06 to 1.79).
Significant increase in confirmed overall response rate (78.9% vs. 36.9%; RR 2.14, 95% CI 0.87 to 3.41).
Significant increase in median progression-free survival 2 (45.2 months vs. 23.1 months; HR 1.89, 95% CI 1.47 to 2.44).
Safety outcomes
No significant difference in treatment-emergent adverse events.
Conclusion
In patients with advanced HER2+ metastatic breast cancer previously treated with taxane and trastuzumab, trastuzumab deruxtecan was superior to trastuzumab emtansine with respect to median progression-free survival.
Reference
Javier Cortés, Sara A Hurvitz, Seock-Ah Im et al. Trastuzumab deruxtecan versus trastuzumab emtansine in HER2-positive metastatic breast cancer: long-term survival analysis of the DESTINY-Breast03 trial. Nat Med. 2024 Jun 2. Online ahead of print.
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