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Advanced NSCLC in Focus: Collaborative Management of EGFR Mutation and ALK Rearrangement Disease : Episode 4

Navigating CNS Disease in EGFR-Mutant NSCLC

July 2, 2025
By Danny Nguyen, MD
Katherine Cunha, MSN, FNP-C
  • Michelle Munroe, APRN
  • Jun Zhang, MD, PhD

Opinion
Video

Panelists discuss how both amivantamab plus lazertinib and osimertinib-based regimens show good central nervous system activity for patients with baseline brain metastases, with treatment choice influenced more by patient-specific factors like bleeding risk and anticoagulation contraindications than by CNS efficacy differences.

EP: 1.Clinical Case: EGFR-Mutant (Exon 19 del) Advanced NSCLC

EP: 2.The Treatment Landscape For Advanced EGFR-Mutant NSCLC

EP: 3.Emerging Insights From MARIPOSA: OS Updates From Amivantamab/Lazertinib in Advanced NSCLC

Now Viewing

EP: 4.Navigating CNS Disease in EGFR-Mutant NSCLC

EP: 5.From Trial to Practice: Integrating Amivantamab/Lazertinib in Advanced NSCLC

EP: 6.Patient Education and IRR Prophylaxis in Practice With Amivantamab/Lazertinib

EP: 7.Managing Dermatologic AEs With Amivantamab/Lazertinib: Updates From the COCOON Clinical Trial

EP: 8.The Multidisciplinary Approach to Care for Advanced NSCLC

EP: 9.Clinical Case: ALK-Positive Advanced NSCLC

EP: 10.Frontline Treatment Decisions in ALK+ NSCLC

EP: 11.Clinical Perspectives and Emerging Updates in Advanced NSCLC

EP: 12.Proactive Care in ALK-Positive NSCLC: Adverse Effect Counseling, Monitoring, and Management

EP: 13.Supporting Patients Through Treatment for Advanced NSCLC

Video content above is prompted by the following:

Central nervous system metastases present a significant challenge in EGFR-mutant non–small cell lung cancer (NSCLC) management, affecting treatment selection and patient outcomes. Both the FLAURA2 and MARIPOSA studies included patients with baseline brain metastases, providing valuable insights into central nervous system (CNS) activity of different treatment regimens. However, clinicians must exercise caution when interpreting subgroup analyses, as these post hoc analyses lack statistical power for definitive conclusions about relative efficacy in the CNS metastases population.

The MARIPOSA study demonstrated consistent benefit from amivantamab plus lazertinib combination therapy regardless of baseline brain metastases status, with patients both with and without CNS disease showing improved outcomes compared to osimertinib monotherapy. In contrast, the FLAURA2 study showed particularly pronounced benefits in patients with brain metastases, suggesting strong CNS penetration and activity of the osimertinib plus chemotherapy combination. At 36 months, approximately 38% of patients treated with amivantamab plus lazertinib remained progression-free in the brain, while the FLAURA2 study reported an intracranial progression-free survival of approximately 30 months.

Patient-specific factors become particularly important when selecting treatment for patients with baseline CNS metastases. For patients with recent brain resection or hemorrhagic metastases, the requirement for anticoagulation with amivantamab may pose safety concerns, making osimertinib-based regimens more appropriate. Additionally, chemotherapy components may interfere with wound healing and cause thrombocytopenia, potentially favoring osimertinib monotherapy in certain clinical scenarios. The key takeaway is that both treatment approaches demonstrate excellent CNS activity, allowing clinicians to select regimens based on individual patient characteristics and safety considerations rather than efficacy concerns alone.

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A subgroup analysis of OS showed that results were favorable with amivantamab plus lazertinib in patients who are Asian.

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September 12th 2025
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Full overall survival results with amivantamab plus lazertinib from the Asia cohort of the MARIPOSA trial will be shared at a future medical conference.

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