A 65-year-old smoker develops a 3 cm peripheral lung mass with pleural puckering. Biopsy shows gland formation, mucin production, and positive TTF-1 and Napsin-A staining. EGFR testing shows exon 19 deletion. Which targeted therapy is preferred?

• A Crizotinib (ALK/ROS1 inhibitor)
• B Osimertinib (third-generation EGFR-TKI) ✓
• C Pembrolizumab (PD-1 inhibitor)
• D Bevacizumab (anti-VEGF)

Explanation

EGFR exon 19 deletions and exon 21 L858R point mutations are the two most common sensitizing EGFR mutations in lung adenocarcinoma; both predict excellent response to EGFR-TKIs. Current guidelines (FLAURA trial) favor osimertinib (third-generation EGFR-TKI) as first-line therapy because it outperforms first-generation (gefitinib, erlotinib) in PFS and OS, and crosses the blood-brain barrier. Crizotinib targets ALK (EML4-ALK fusion, not EGFR mutation). Pembrolizumab is preferred for PD-L1-high, driver-mutation-negative NSCLC. Bevacizumab is used as an add-on but not primary driver-targeted therapy.

Reference: Robbins & Cotran Pathologic Basis of Disease, 10th ed.

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Written and medically reviewed by the StethoPrep medical team.