Erlotinib — Drug Monograph
Brand names: Tarceva
Drug class: Tyrosine Kinase Inhibitor
Mechanism of Action
First-generation reversible EGFR (HER1/ErbB1) tyrosine kinase inhibitor that competitively binds the intracellular ATP-binding domain of EGFR, blocking auto-phosphorylation and downstream MAPK, PI3K/AKT, and STAT signaling pathways. Active against EGFR exon 19 deletions and exon 21 L858R mutations in NSCLC. Also exerts antitumor effects in pancreatic cancer via EGFR pathway blockade, though efficacy is modest.
FDA Indications
- Locally advanced or metastatic NSCLC after failure of at least one prior chemotherapy regimen (FDA approved November 2004; BR.21 trial: OS benefit vs best supportive care in unselected NSCLC)
- First-line treatment of metastatic NSCLC with EGFR exon 19 deletions or exon 21 L858R substitution mutations (FDA approved May 2013; EURTAC trial: PFS HR 0.37)
- Locally advanced, unresectable, or metastatic pancreatic cancer in combination with gemcitabine (FDA approved November 2005; NCIC CTG PA.3 trial: OS HR 0.82)
Common Side Effects
- Acneiform/papulopustular skin rash (~75% — severity correlates with clinical efficacy)
- Diarrhea
- Fatigue
- Anorexia
- Nausea
- Paronychia
- Dry skin and mucositis
- Elevated liver enzymes
Clinical Pearl
Rash severity is a validated pharmacodynamic marker of EGFR inhibition with erlotinib — patients who develop acneiform rash Grade ≥2 have consistently superior OS and PFS compared to those without rash, in both NSCLC and pancreatic cancer trials. Smoking is a critical PK confounder: tobacco smoke induces CYP1A2, reducing erlotinib plasma levels by up to 66%; smokers may require dose escalation to 300 mg. The benefit in pancreatic cancer, while statistically significant (OS HR 0.82), translates…
Related Therapies & Mechanisms
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