Evolving Strategies in EGFR-Mutated NSCLC: Optimizing CNS Control and Managing Treatment-Related Toxicities

Misako Nagasaka, MD, PhD, Dr. Nagasaka introduces the panel and outlines the session’s focus on applying new EGFR-mutated NSCLC data to practice, with emphasis on CNS control and toxicity prevention.

Experts discuss applying emerging evidence from MARIPOSA and FLAURA2 to first-line decision-making in EGFR-mutated disease.

The panel examines a 59-year-old woman with small brain metastases, addressing therapy selection to balance CNS control, survival, and quality of life.

The physicians share real-world imaging schedules, triggers for adding local therapy, and lessons from serial MRI data in the MARIPOSA trial.

Discussion centers on early dermatologic AEs with amivantamab plus lazertinib, emphasizing prevention protocols and staff education.

The panel reviews components of the COCOON prophylactic regimen and the safe use of temporary dose modifications to maintain adherence.

The conversation shifts to how dual EGFR-MET inhibition reduces resistance mutations and molecular heterogeneity compared with osimertinib monotherapy.

A second case illustrates clinical decision-making after progression on osimertinib, highlighting diagnostic re-biopsy and ctDNA testing.

The panel explores integrating molecular data to guide therapy selection and optimize sequencing strategies after resistance emerges.

Experts debate when to introduce chemotherapy, how to manage its cumulative toxicity, and how to de-escalate maintenance regimens.

The discussion underscores the role of multidisciplinary coordination in maintaining adherence, quality of life, and long-term therapeutic benefit.

Misako Nagasaka, MD, PhD, summarizes the key takeaways: proactive AE management, CNS vigilance, and strategic sequencing as hallmarks of modern care for EGFR-mutant NSCLC.