Datopotamab Deruxtecan (Dato-DXd) vs Chemotherapy for Patients with Metastatic HR+/HER2– BC: Primary Results from the Randomized Phase III TROPION-Breast01 Trial

Datopotamab deruxtecan (Dato-DXd) vs Chemotherapy in Previously-treated Inoperable or Metastatic Hormone Receptor-positive, HER2-negative (HR+/HER2–) Breast Cancer: Primary Results from the Randomized Phase 3 TROPION-Breast01 Trial

Background

• HR+/HER2– breast cancer is the most common subtype of breast cancer
• Chemotherapy is utilized widely for management of endocrine-resistant HR+/HER2– MBC,
  but is associated with low response rate, poor prognosis, and significant toxicity
• TROP2-directed ADCs can have significant toxicities
• Dato-DXd is a unique TROP2-directed ADC demonstrating promising antitumor activity and a manageable safety profile

Study Design

• TROPION-Breast01 is a randomized, phase 3, global study comparing dato-DXd to chemotherapy in HR+/HER2– breast cancer
  • Patients were previously treated with 1-2 lines of chemotherapy, experienced progression on ET, and showed ECOG PS 0 or 1
  • Randomization was stratified by lines of chemotherapy, geographic location, and previous CDK4/6 inhibitor exposure
  • Randomization occurred 1:1 to dato-DXd or investigator’s choice chemotherapy
• Dual primary endpoints included PFS by BICR per RECIST v1.1 and OS
• Key secondary endpoints included ORR, PFS, and safety

Results

• TROPION-Breast01 demonstrated that Dato-DXd provides both improved efficacy and safety compared with ICC for patients with HR+/HER2– disease
• TROPION-Breast01 met its dual primary PFS endpoint, demonstrating statistically significant and clinically meaningful improvement in PFS with Dato-DXd compared with ICC
• Overall, Dato-DXd demonstrated a favorable and manageable safety profile, with no new safety signals
• Results support Dato-DXd as a potential new therapeutic option for patients with metastatic HR+/HER2– breast cancer