Selecting First-Line Therapy for EGFR-Mutated NSCLC

This Around the Practice installment focuses on the translation of emerging clinical data into real-world practice for EGFR-mutated non–small cell lung cancer. The series begins with Misako Nagasaka, MD, PhD, moderating a panel that contextualizes recent trial results—including MARIPOSA, FLAURA2, and WCLC/ESMO 2025 findings—within the modern frontline treatment landscape. Using 2 detailed patient profiles, the discussion highlights how first-line regimens are selected based on molecular features, comorbidities, and the presence of central nervous system (CNS) disease. The experts compare outcomes between amivantamab plus lazertinib and osimertinib-based regimens, weighing survival benefits, CNS efficacy, and quality-of-life considerations.

As the conversation deepens, the panel explores practical management of treatment-related toxicities and CNS control. They outline surveillance protocols for brain metastases, discuss MRI monitoring intervals, and assess when to use local therapies such as stereotactic radiosurgery. The dermatologic adverse events common with amivantamab plus lazertinib are addressed in detail, emphasizing early use of the COCOON prophylactic regimen and the reassurance that temporary dose modifications do not reduce long-term benefit. The clinicians share firsthand strategies for integrating toxicity management seamlessly into care workflows while maintaining efficacy.

In the final portion, the discussion transitions to sequencing and management beyond the first line. Panelists analyze diagnostic options such as ctDNA vs tissue biopsy to identify actionable resistance mechanisms, particularly MET amplification and EGFR C797S mutations. They also compare the toxicity patterns of targeted therapy versus chemotherapy-containing regimens, debating the timing of chemotherapy introduction to limit cumulative adverse effects. Closing reflections highlight the value of multidisciplinary collaboration, patient education, and proactive monitoring as essential elements in optimizing long-term outcomes and preserving patient quality of life.