Forty-Seven-Year-Old Woman With Recurrent HER2+  Breast Cancer and Brain Metastases

Clinical Brief: DESTINY-Breast12 and Brain Metastases Management - Segment 5

Key Themes:

• DESTINY-Breast12 Study Design: Phase 3b/4 multicenter study with 2 cohorts – patients with and without baseline brain metastases
• Central Nervous System (CNS) Efficacy Results: Trastuzumab deruxtecan (T-DXd) demonstrated over 70% CNS overall response rate in patients with brain metastases
• Similar Efficacy Regardless of Brain Metastasis Status: T-DXd showed comparable activity in patients with and without brain metastases

Key Points for Physicians:

• DESTINY-Breast12 enrolled 263 patients with baseline brain metastases and 241 without
• The 12-month progression-free survival (PFS) rate was approximately 60% overall, with a median PFS of 17.3 months
• CNS response rates were slightly better for stable brain metastases but impressive across both stable and active brain disease
• Fatal interstitial lung disease cases occurred despite intensive monitoring

Notable Insights:

• The data support T-DXd use in patients with HER2+ disease with brain metastases, regardless of whether it is stable or active
• The study results align with other data sets demonstrating T-DXd’s activity against brain metastases
• Historical paradigms about drug efficacy in HER2+ disease and CNS penetration are being challenged by newer clinical data

Clinical Significance:

DESTINY-Breast12 provides robust evidence supporting the use of T-DXd in patients with HER2+ disease with brain metastases, potentially changing treatment sequencing decisions and highlighting the evolving understanding of CNS-directed therapy in this patient population.