CNS Metastases and Combination Therapy for EGFR-Mutant NSCLC

This segment returns to the discussion of CNS metastases in patients with EGFR-mutant mNSCLC and the benefits of combination therapy. The panel emphasizes that patients with brain involvement, even if asymptomatic, derive significant benefit from regimens such as amivantamab plus lazertinib, which demonstrate superior intracranial progression-free survival compared to osimertinib alone. Experts discuss clinical strategies for monitoring CNS disease, including early MRI follow-up to ensure timely detection of response or progression. The discussion reiterates that combination therapies offer durable intracranial control, doubling progression-free survival in patients with baseline brain metastases, and that careful monitoring is necessary to optimize outcomes. Patient education is highlighted as critical, ensuring that individuals understand both efficacy and potential side effects. The panel emphasizes that early, aggressive intervention, supported by robust CNS-active agents, can meaningfully alter the long-term disease trajectory. Considerations for balancing therapy intensity with tolerability and quality-of-life priorities are also discussed. Overall, this segment reinforces that CNS involvement should influence first-line therapy selection, and that combination regimens provide a clear advantage in both systemic and intracranial disease control.