Erlotinib

Erlotinib: This EGFR Drug Could Change Lung Cancer Forever

Erlotinib is a tyrosine kinase inhibitor used for the treatment of non-small cell lung cancer (NSCLC) and pancreatic cancer. It works by targeting the epidermal growth factor receptor (EGFR) to inhibit tumor growth and progression.

Core Indications

  • Non-Small Cell Lung Cancer (NSCLC)

    • First-line treatment for EGFR mutation-positive metastatic NSCLC (exon 19 deletions/exon 21 L858R).

    • Maintenance therapy after platinum-based chemo in unselected advanced NSCLC.

  • Pancreatic Cancer

    • Combined with gemcitabine for locally advanced/metastatic disease (after failure of prior chemotherapy).

Mechanism of Action

  • EGFR Tyrosine Kinase Inhibitor (TKI):
    Blocks the intracellular tyrosine kinase domain of Epidermal Growth Factor Receptor (EGFR), inhibiting:
    → Tumor cell proliferation
    → Angiogenesis
    → Metastasis

Biomarker Testing Requirement

  • Mandatory for NSCLC: EGFR mutation testing (tissue biopsy or liquid ctDNA) before initiation.

  • Not required for pancreatic cancer (used empirically in combination therapy).

 

Dosing & Administration

Indication Dosing Key Instructions
NSCLC (monotherapy) 150 mg orally once daily Take on an empty stomach (1 hour before/2 hours after food).
Pancreatic (with gemcitabine) 100 mg orally once daily + gemcitabine Same fasting requirement.

 

Common Side Effects (>20%)

Side Effect Management
Acneiform Rash (75%) Topical steroids/antibiotics; avoid sun; dose reduction if severe.
Diarrhea (54%) Loperamide; hydration; dose hold if severe.
Fatigue (52%) Activity pacing; rule out other causes.
Anorexia (33%) Nutritional support; small frequent meals.
Nail Changes (14-24%) Moisturize; avoid trauma.

 Serious Risks

  • Interstitial Lung Disease (ILD):
    Incidence: ~1.1%; fatal in 1/3 of cases.
    → Symptoms: Acute dyspnea, cough, fever → Stop erlotinib immediately and investigate.

  • Hepatotoxicity:
    Monitor LFTs monthly; fatal hepatic/renal failure reported.

  • GI Perforation: Rare but high mortality.

  • Ocular Disorders: Corneal ulcers/perforation (report eye pain/redness).

Drug Interactions

  • Avoid PPIs/H₂ Blockers: ↑ Gastric pH → reduces erlotinib absorption by 50%.
    → Use antacids timed separately (e.g., 2 hours before/after erlotinib).

  • CYP3A4 Inducers (e.g., rifampin): ↓ Erlotinib levels → risk of treatment failure.

  • CYP3A4 Inhibitors (e.g., ketoconazole): ↑ Erlotinib levels → risk of toxicity.

  • Warfarin: ↑ INR monitoring (bleeding risk).

Key Patient Counseling Points

  1. Take on empty stomach: Critical for absorption.

  2. Rash ≠ allergy: Often indicates drug activity; don’t stop without consulting doctor.

  3. Report immediately:

    • Shortness of breath/new cough

    • Severe diarrhea/abdominal pain

    • Jaundice/dark urine

    • Eye changes

  4. Avoid sun exposure: Use SPF 30+ and protective clothing.

 

Clinical Efficacy

  • NSCLC (EGFR+)

    • Response Rate: 60-80% vs. chemo (30%).

    • Median PFS: 9.7-13.1 months (vs. 4.6-6.9 months with chemo).

  • Pancreatic Cancer

    • Adds ~12 days survival benefit vs. gemcitabine alone (OS: 6.24 vs 5.91 months).

Summary

Erlotinib remains a cornerstone for EGFR-mutant NSCLC and adjunct in pancreatic cancer. Strict adherence to fasting dosing, proactive toxicity management (especially rash/ILD), and avoiding pH-altering drugs are critical for optimal outcomes. Biomarker testing is essential in NSCLC to identify responders.