Dr. Seema Nagpal, clinical professor of neurology in the Division of Neuro-oncology at Stanford University, and Dr. Laura Alder, assistant professor of thoracic medical oncology at Duke University, discuss CNS disease management in EGFR-mutated non-small cell lung cancer (NSCLC). The program covers first-line CNS efficacy data from the FLAURA2 and MARIPOSA trials, CNS surveillance standards and barriers to consistent practice, a clinical case of CNS-only progression on osimertinib, second-line sequencing across COMPEL, TROPION-Lung01 and TROPION-Lung05, and MARIPOSA-2, and emerging agents including datopotamab deruxtecan, ivonesimab, and izalontamab brengitecan. Critical gaps in CNS endpoint reporting, including treated versus untreated lesions, leptomeningeal disease inclusion, response criteria heterogeneity, are examined. Leptomeningeal disease management is discussed in depth, including osimertinib dose escalation and pulse dosing, amivantamab-lazertinib sequencing, intrathecal therapies, proton craniospinal irradiation, and cerebrospinal fluid liquid biopsy including circulating tumor cells. Strategies for community clinicians without access to specialized interventions are emphasized throughout.
Dr. Nagpal reviews frontline CNS data from the FLAURA2 and MARIPOSA trials, noting the importance of CNS-specific endpoints now being routinely incorporated into NSCLC clinical trials. Both trials enrolled patients with stable, predominantly pre-treated brain metastases.
Dr. Alder raises the inconsistency of CNS surveillance across practice settings in EGFR-mutated NSCLC, noting that even within the FLAURA2 and MARIPOSA trials, brain MRI schedules were not uniform. She asks Dr. Nagpal to address evidence-based surveillance recommendations and the barriers to implementing them.
Dr. Nagpal presents a 58-year-old female non-smoker with stage IVB lung adenocarcinoma, EGFR L858R mutation, and TP53 co-mutation who maintained partial systemic response on first-line osimertinib for approximately 3.5 years.
Dr. Nagpal asks how Dr. Alder synthesizes the growing CNS evidence base for second-line therapy after osimertinib progression, referencing COMPEL, TROPION-Lung01 and TROPION-Lung05, MARIPOSA-2, and real-world sequencing data from ASCO 2026.
The discussion addresses emerging second-line options and systematic limitations in CNS endpoint reporting across trials.
Dr. Nagpal outlines her treatment algorithm for leptomeningeal disease (LMD) in EGFR-mutated NSCLC, framing her approach from a neuro-oncology perspective that prioritizes preserving brain function, sometimes over full disease eradication.
Dr. Alder asks how clinicians without access to proton therapy, intrathecal treatment, or specialized neuro-oncology consultation should approach LMD and CNS disease, and what infrastructure changes would most improve outcomes.
