Navigating CNS Disease in EGFR-Mutant NSCLC
Panelists discuss how both amivantamab plus lazertinib and osimertinib-based regimens show good central nervous system (CNS) activity for patients with baseline brain metastases, with treatment choice influenced more by patient-specific factors such as bleeding risk and anticoagulation contraindications than by CNS efficacy differences.
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CNS metastases present a significant challenge in EGFR-mutant NSCLC management, affecting treatment selection and patient outcomes. Both the FLAURA2 and MARIPOSA studies included patients with baseline brain metastases, providing valuable insights into 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 findings 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 with osimertinib monotherapy. In contrast, the FLAURA2 study findings 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, whereas the study findings 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.
