EGFR-Mutant Non-Small-Cell Lung Cancer Intracranial Metastases Treatment

• Furmonertinib in uncommon EGFR-mutated non-small cell lung cancer with central nervous system metastases: A retrospective cohort study
• Efficacy analysis of brain radiotherapy in EGFR mutation non-small cell lung cancer with brain metastasis: a retrospective study
• Osimertinib as Salvage Therapy in Advanced Non-Small Cell Lung Cancer After Aumolertinib Resistance With T790M Mutation: A Case Report
• The climb toward intracranial efficacy: Zorifertinib in EGFR-mutant NSCLC with CNS metastases in the EVEREST trial
• Effects of EGFR-TKIs combined with intracranial radiotherapy in EGFR-mutant non-small cell lung cancer patients with brain metastases: a retrospective multi-institutional analysis
• Intrathecal pemetrexed improves survival outcomes in previously treated EGFR-mutant advanced non-small-cell lung cancer with leptomeningeal metastases
• Optimal intervention timing for craniocerebral radiotherapy in EGFR mutant lung adenocarcinoma patients with brain metastases
• Emerging Therapies for Brain Metastases in NSCLC, Breast Cancer, and Melanoma: A Critical Review

🧠 Summary: Treatment of brain metastases in EGFR-mutant NSCLC is centered around Epidermal growth factor receptor tyrosine kinase inhibitors with CNS penetration, especially osimertinib. Local therapy is considered based on symptoms and extent of disease.

1. EGFR Tyrosine Kinase Inhibitors (TKIs)

• Osimertinib – 3rd-generation TKI
  • Highly effective against common EGFR mutations and T790M
  • Excellent CNS penetration (FLAURA trial)
  • Preferred first-line treatment
• Older TKIs – Erlotinib, Afatinib, Gefitinib (lower CNS activity)
• New agents under investigation – Lazertinib, Furmonertinib

2. Local Therapy for Brain Metastases

• SRS (Stereotactic Radiosurgery) – for ≤5 lesions or symptomatic ones
• WBRT (Whole Brain Radiotherapy) – reserved for extensive CNS disease or progression
• Surgical resection – rare, used in case of mass effect or diagnostic uncertainty

3. Surveillance & Resistance

• Follow-up: Brain MRI every 2–3 months during treatment
• Common resistance: C797S mutation, MET amplification
• Next steps: Biopsy (liquid or tissue), clinical trial enrollment, consider newer generation TKIs

4. Emerging Therapies & Clinical Trials

• Combination therapies (e.g., osimertinib + bevacizumab)
• Fourth-gen TKIs under investigation
• Antibody-drug conjugates (ADCs)
• Trials for C797S and other resistance mechanisms

📋 Summary Table:

📌 Tip: Always evaluate patients in a multidisciplinary tumor board to personalize treatment — involving oncology, radiation oncology, radiology, and neurosurgery.