Disease Reassessment at First Progression and Treatment Options for Resistance Mechanisms in EGFR-mutant NSCLC

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Subsequent Therapy After Progression

Key Themes:

• Biomarker-Based Approach: Value of repeat biopsies (tissue or liquid) to identify resistance mechanisms such as MET amplification
• Treatment Options: Discussion of MARIPOSA-2 regimen (amivantamab plus chemotherapy), VEGF inhibitors, and emerging antibody-drug conjugates
• Histologic Transformation: Importance of identifying small cell transformation, which requires different treatment approaches

Notable Insights:

• Dr Piotrowska: Advocates for tissue biopsies at progression when possible, stating “histologic transformation, particularly after osimertinib monotherapy... is still a real challenge” and can dramatically change treatment selection. She estimates MET alterations may be present in “25 to 30% of patients.”
• Dr Dietrich: Noted that “both lazertinib and osimertinib are such good EGFR inhibitors that EGFR on-target resistance escape is incredibly rare.” He highlighted that the main treatment decisions affecting outcomes are made in the first-line setting, with later lines being “on the defense.”