HER2-positive intracranial metastases treatment

• Stereotactic radiosurgery for HER2-positive breast cancer brain metastases: prognostic factors and the evolving role of anti-HER2 therapies
• Advances in Targeted Therapy for Brain Metastases in Human Epidermal Growth Factor Receptor 2 (HER2)-Positive Breast Cancer: A Focus on ADCs and TKIs
• Efficacy and safety of trastuzumab deruxtecan in HER2-positive breast cancer patients with brain metastases after failure of pyrotinib-based therapy
• Breast Cancer Brain Metastases: A Neurosurgical Point of View From a Single-Center Experience
• Excellent Response to Trastuzumab Deruxtecan of a Large Medullary Metastasis from Human Epidermal Growth Factor Receptor 2-Positive Breast Cancer: A Case Report
• Factors associated with local failure after stereotactic radiation to the surgical bed of patients with a single breast cancer metastasis
• Treatment Outcome of Brain Metastases from Breast Cancer Following Gamma Knife Radiosurgery: A Retrospective Study in Vietnam
• Efficacy of disitamab vedotin (RC48) for previously treated human epidermal growth factor receptor 2-positive breast cancer with symptomatic brain metastases: a case report and review of the literature

• Indicated for large, symptomatic, or surgically accessible metastases.
• Improves neurological symptoms and reduces tumor burden.

• Preferred for patients with ≤ 4 metastases or selected cases with more.
• Delivers high-dose radiation precisely, sparing normal tissue.
• Can be combined with systemic therapy.

• Used for multiple metastases but less favored due to neurotoxicity.
• Consider hippocampal-sparing WBRT with memantine to reduce cognitive decline.

• Tucatinib + Trastuzumab + Capecitabine (HER2CLIMB Trial)
  • Tucatinib is a selective HER2 TKI with CNS penetration.
  • Improves progression-free survival (PFS) and overall survival (OS).

• Trastuzumab Deruxtecan (T-DXd, Enhertu)
  • Antibody-drug conjugate with high intracranial activity.
  • Effective even in progressive brain metastases.

• Lapatinib + Capecitabine
  • Historically used, but less effective than tucatinib.
  • Option for patients who cannot access newer agents.

• Pyrotinib + Capecitabine (China-based studies)
  • Pan-HER TKI with intracranial efficacy.
  • Limited global availability.

• Neratinib + Capecitabine
  • TKI with CNS penetration.
  • Consider in progressive brain metastases after other TKIs.

• Radiation + HER2-targeted therapy (e.g., SRS + tucatinib-based regimen).
• Immunotherapy (e.g., pembrolizumab) under investigation for synergy with HER2-directed agents.

• Intrathecal HER2-directed therapy (experimental, for leptomeningeal disease).
• Chimeric antigen receptor (CAR) T-cell therapy targeting HER2 (preclinical/early trials).
• Blood-brain barrier modulation strategies to improve drug delivery.

A multimodal approach combining systemic therapy (especially tucatinib-based regimens), SRS, and possibly surgery provides the best outcomes. Trastuzumab deruxtecan is a promising option for progressive disease. Clinical trials continue to refine treatment strategies.