Datopotamab deruxtecan (Dato-DXd, Datroway) exploratory brain metastases findings from Phase 3 TROPION-Breast02 in 1L mTNBC patients

Exploratory brain metastases subgroup findings from P3 TROPION-Breast02 suggest datopotamab deruxtecan CNS activity in 1L mTNBC (IO-ineligible) patients with asymptomatic brain metastases. While limited by small sample size and baseline imbalances, the data may increase confidence in Dato-DXd's activity in this underserved population and contribute to its emerging evidence package following recent global approvals (#LBA96)

• Key Takeaways/Potential Implications  
  • Exploratory analysis of patients with brain metastases (N=61) showed improved CNS outcomes with Dato-DXd vs ICC, including longer CNS PFS (9.5 vs 2.6 mo; HR: 0.27) and higher intracranial cORR (63% vs 38%).
  • Systemic efficacy also favored Dato-DXd with improvement in PFS (7.7 vs 3.5 mo; HR: 0.37) and OS (13.5 vs 10.7 mo; HR: 0.55), suggesting intracranial activity was accompanied by broader disease control.
    • Greater numerical benefits were highlighted in the previously untreated brain metastases cohort, with PFS (7.7 vs 2.6 mo; HR: 0.29) and OS (11.6 vs 9.1 mo; HR: 0.35), although subgroup sizes were small (N=30)
  • The discussant highlighted the caveats that the analysis was limited to patients with asymptomatic brain metastases and cautioned against extrapolating findings to symptomatic population
    • Interpretation was noted to be further constrained by the small sample size (N=61), and baseline imbalances (median age: 62 vs 55 years; DFI ≤12 mo: 17% vs 31%) with more aggressive disease in the ICC arm
  • These findings may strengthen HCP confidence in Dato-DXd for patients with brain metastases in the TB-02 setting
• Study Information 
  • P3 TROPION-Breast02: Dato-DXd vs ICC in 1L mTNBC ineligible for IO; 1EP: PFS/OS
  • N= 644 (323 vs 321)
    • Brain mets subgroup: N=61 (35 vs 26)
      • Previously untreated brain mets: 19 vs 11
      • Previously treated brain mets: 16 vs 15
• Efficacy (Dato-DXd vs CT in brain mets cohort)
  • CNS mPFS: 9.5 vs 2.6 mo (HR: 0.27)
  • Systemic mPFS: 7.7 vs 3.5 mo (HR: 0.37)
    • Previously treated: 6.8 vs 3.5 mo (HR: 0.43)
    • Previously untreated: 7.7 vs 2.6 mo (HR: 0.29)
  • OS: 13.5 vs 10.7 mo (HR: 0.55)
    • Previously treated: 19.3 vs 12.8 mo (HR: 0.77)
    • Previously untreated: 11.6 vs 9.1 mo (HR: 0.35)
  • Systemic cORR: 63% vs 19% (OR: 7.11)
    • Previously treated: 63% vs 33%
    • Previously untreated: 63% vs 0%
  • Intracranial cORR with measurable CNS disease: 63% vs 38%
• Safety
  • No subgroup-specific safety data presented