Seema Nagpal, MD

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.

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.

The discussion addresses emerging second-line options and systematic limitations in CNS endpoint reporting across trials.

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.

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. 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 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.

Seema Nagpal, MD, discusses the FDA approval of vorasidenib for patients with astrocytoma or oligodendroglioma harboring IDH1 or IDH2 mutations.