DESTINY-Breast04
Trial question
What is the role of trastuzumab deruxtecan in patients with HER2-low metastatic breast cancer?
Study design
Multi-center
Open label
RCT
Population
557 female patients.
Inclusion criteria: patients with HER2-low unresectable or metastatic breast cancer.
Key exclusion criteria: history of noninfectious ILD treated with corticosteroids; suspected ILD on imaging; previous treatment with anti-HER2.
Interventions
N=373 trastuzumab deruxtecan (intravenous administration of 100 mg in 5 mL solution).
N=184 chemotherapy (physician's choice of single-agent chemotherapy, such as capecitabine, eribulin, gemcitabine, paclitaxel, or nab-paclitaxel).
Primary outcome
Progression-free survival in patients with hormone receptor-positive disease
10.1 months
5.4 months
10.1 months
7.6 months
5.0 months
2.5 months
0.0 months
Trastuzumab
deruxtecan
Chemotherapy
Significant
increase ▲
Significant increase in progression-free survival in patients with HR+ disease (10.1 months vs. 5.4 months; HR 1.96, 96% CI 1.56 to 2.5).
Secondary outcomes
Significant increase in progression-free survival (9.9 months vs. 5.1 months; HR 2, 95% CI 1.58 to 2.5).
Significant increase in overall survival in patients with HR+ disease (23.9 months vs. 17.5 months; AD 6.4 months, 95% CI 2.18 to 10.62).
Significant increase in overall survival (23.4 months vs. 16.8 months; AD 6.6 months, 95% CI 2.68 to 10.52).
Safety outcomes
No significant difference in serious adverse events and adverse events ≥ grade 3.
Conclusion
In patients with HER2-low unresectable or metastatic breast cancer, trastuzumab deruxtecan was superior to chemotherapy with respect to a progression-free survival in patients with HR+ disease.
Reference
Shanu Modi, William Jacot, Toshinari Yamashita et al. Trastuzumab Deruxtecan in Previously Treated HER2-Low Advanced Breast Cancer. N Engl J Med. 2022 Jul 7;387(1):9-20.
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