6/28/23, 1:16 AM DESTINY-Breast04 Pathway Feedback Search Clinical Topics Home Studies DESTINY Breast04 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 glucocorticoids; 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 physician's choice of chemotherapy (capecitabine, eribulin, gemcitabine, paclitaxel, or nab- paclitaxel) Primary outcome Progression-free survival among patients with hormone receptor-positive disease 10.1 months 10.1 7.6 months 5.4 5.0 months 2.5 months Significant increase 0.0 months Trastuzumab deruxtecan Physician's choice of chemotherapy Significant increase in progression-free survival among patients with hormone receptor-positive disease (10.1 months vs. 5.4 months; HR 1.96, 96% CI 1.56 to 2.5) Secondary outcomes https://web.pathway.md/studies/rectQ7L8t5vgjhemq 1/2 6/28/23, 1:16 AM DESTINY-Breast04 Pathway Significant increase in progression-free survival among all patients (9.9 months vs. 5.1 months; HR 2, 95% CI 1.58 to 2.5) Significant increase in overall survival in the hormone receptor-positive cohort (23.9 months vs. 17.5 months; AD 6.4 months, 95% CI 2.18 to 10.62) Significant increase in overall survival in all patients (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 physician's choice of chemotherapy with respect to a progression-free survival among patients with hormone receptor-positive 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. Open reference URL https://web.pathway.md/studies/rectQ7L8t5vgjhemq 2/2