Critical Questions in Choosing EGFR-Targeted Therapies for NSCLC

Christine M. Lovly, MD, PhD, FASCO; and Balazs Halmos, MD, MS, discuss how the first-line treatment landscape for EGFR-mutated non–small cell lung cancer (NSCLC) is evolving, with osimertinib as the standard, while combinations are explored to enhance efficacy. FLAURA, FLAURA2, and MARIPOSA trials inform treatment selection, balancing efficacy, safety, and CNS activity. Patient factors such as disease burden and resistance guide sequencing decisions, with MARIPOSA-2 and PALOMA-3 shaping second-line choices. Managing adverse events in combination regimens remains key. Unmet needs include overcoming resistance and improving long-term outcomes.

EP. 1: Brief Overview of the Treatment Landscape of First-Line EGFRm NSCLC

March 31st 2025

Panelists discuss how the first-line treatment landscape for EGFR-mutated non–small cell lung cancer (NSCLC) primarily includes EGFR tyrosine kinase inhibitors, with osimertinib as the preferred monotherapy due to its efficacy and central nervous system penetration. Balancing efficacy and safety remain challenging, particularly regarding resistance and adverse effects. Although osimertinib monotherapy is widely used, combination strategies (eg, chemotherapy or antiangiogenic agents) are being explored to enhance outcomes. Treatment decisions are guided by mutation type, patient factors, and emerging clinical data.

EP. 2: FLAURA, FLAURA2, and MARIPOSA: Key Takeaways to Impact First-Line Treatment Approach

March 31st 2025

Panelists discuss how the FLAURA, FLAURA2, and MARIPOSA trials have reshaped first-line therapy for EGFR-mutant non–small cell lung cancer. FLAURA established osimertinib as superior to first-generation tyrosine kinase inhibitors. FLAURA2 showed added benefit with chemotherapy. MARIPOSA highlighted amivantamab-lazertinib as a strong alternative, refining treatment choices.

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