First-Line CNS Efficacy in EGFR-Mutated NSCLC: FLAURA2 and MARIPOSA Data

In FLAURA2, adding carboplatin-pemetrexed chemotherapy to osimertinib improved systemic responses that translated to intracranial benefit across both measurable and non-target CNS lesions. Crucially, the presence of brain metastases did not attenuate overall response, and patients with brain metastases may have derived proportionally greater benefit over osimertinib monotherapy than those without, suggesting particular CNS activity for the chemotherapy-osimertinib combination. In MARIPOSA, amivantamab-lazertinib similarly demonstrated benefit over osimertinib monotherapy, including in patients with CNS involvement, though Dr. Nagpal notes the published FLAURA2 papers contain more granular CNS-specific data than the MARIPOSA papers, and additional CNS response data from Helena Yu's work further supports CNS activity for osimertinib-based combinations.

Both regimens now hold NCCN Category 1 designation. In practice, both panelists favor FLAURA2-based therapy (carboplatin-pemetrexed-osimertinib) for most patients given the more manageable toxicity profile compared with amivantamab, particularly infusion reactions and rash, though Dr. Alder acknowledges that the subcutaneous amivantamab formulation reduces infusion-related burden. Both emphasize individualized selection based on patient goals, comorbidities, and treatment logistics, noting that without head-to-head CNS data, neither regimen can be declared superior for intracranial control.