Key Considerations When Selecting EGFR Inhibitor Treatments in NSCLC - Episode 5
Disease Reassessment at First Progression and Treatment Options for Resistance Mechanisms in EGFR-mutant NSCLC
Panelists discuss how subsequent therapy after initial disease progression should consider patient symptomatology, biomarker testing through tissue or liquid biopsies, and potential treatment options including MET-targeted approaches or chemotherapy combinations.
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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.”
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