Gefitinib — Drug Monograph

Brand names: Iressa

Drug class: Tyrosine Kinase Inhibitor

Mechanism of Action

First-generation reversible EGFR (epidermal growth factor receptor / ErbB1 / HER1) tyrosine kinase inhibitor. Competitively binds the ATP-binding pocket of EGFR, blocking autophosphorylation and downstream signaling through MAPK, PI3K/AKT, and STAT3 pathways. Most active against EGFR exon 19 deletions and exon 21 L858R point mutations, which are the two most common activating EGFR mutations in NSCLC.

FDA Indications

• First-line treatment of patients with metastatic NSCLC whose tumors have EGFR exon 19 deletions or exon 21 L858R substitution mutations — FDA approved July 2015 (IPASS trial: PFS HR 0.48 vs carboplatin+paclitaxel in EGFR-mutated patients)

Common Side Effects

• Acneiform/papulopustular skin rash (approximately 40–50%)
• Diarrhea
• Paronychia (nail inflammation)
• Dry skin and mucous membranes
• Nausea
• Anorexia
• Elevated liver enzymes

Clinical Pearl

Gefitinib has a controversial FDA history: originally approved in 2003 under accelerated approval, it was restricted in 2005 after the ISEL trial failed to show OS benefit in unselected patients; it was re-approved in 2015 specifically for EGFR-mutated NSCLC, demonstrating that biomarker selection is critical. Acneiform rash is a pharmacodynamic marker of EGFR inhibition — patients who develop rash have consistently better outcomes. The incidence of ILD/pneumonitis is notably higher in East…

Related Therapies & Mechanisms

• Afatinib (Gilotrif) — Tyrosine Kinase Inhibitor · NSCLC
• Alectinib (Alecensa) — Tyrosine Kinase Inhibitor · NSCLC
• Capmatinib (Tabrecta) — Tyrosine Kinase Inhibitor · NSCLC
• Dabrafenib (Tafinlar) — Tyrosine Kinase Inhibitor · NSCLC