EGFR mutated NSCLC: Treatment Advances and Highlights from ASCO 2025 - Episode 5
Panelists discuss the evolving management of CNS metastases in EGFR-mutant lung cancer, highlighting how third-generation TKIs and combination regimens from the FLORA and Mariposa trials delay CNS progression and reduce new brain metastases, supporting a shift away from upfront radiation in asymptomatic patients.
When managing CNS metastases in EGFR-mutant lung cancer, the approach has evolved significantly over recent years. Early generation TKIs showed some CNS activity, but radiation was often used upfront. Now, with more effective agents, especially third-generation TKIs, the practice has shifted to delaying local CNS therapy in asymptomatic patients with limited brain disease, focusing instead on systemic treatment to control CNS involvement and preserve quality of life. Both the FLORA and Mariposa trials incorporated rigorous CNS endpoints, including mandatory brain MRIs at baseline and throughout treatment—something rarely feasible in routine practice but very informative for understanding CNS disease progression.
The CNS data from these studies are encouraging, showing a clear reduction in incidence of new brain metastases and progression of existing CNS disease compared to osimertinib alone. While it’s difficult to directly compare these two trials, both demonstrate a meaningful CNS benefit with intensified regimens. Notably, patients with baseline brain metastases remain a high-risk group with median progression-free survival around 13 to 14 months—significantly lower than the 18 to 19 months seen in overall populations—highlighting the need for improved strategies.
Regarding the Mariposa trial, the rigorous CNS monitoring and observed delay in CNS progression suggest that its combination regimen provides adequate control for patients with brain metastases, especially when coupled with careful clinical surveillance. This supports considering Mariposa’s regimen as a frontline option in this subgroup.