Erlotinib vs Gefitinib

## Overview

Erlotinib and gefitinib are both first-generation reversible EGFR TKIs with very similar mechanisms and clinical profiles. Erlotinib has a unique indication in pancreatic cancer; gefitinib was the first EGFR TKI approved. Both have largely been supplanted by osimertinib for first-line EGFR-mutated NSCLC.

## Mechanism of Action

Both are ATP-competitive reversible inhibitors of EGFR tyrosine kinase. They have nearly identical mechanisms and overlapping resistance profiles (primarily T790M mutation).

## Pharmacokinetics

Erlotinib: ~60% bioavailability (food increases absorption ~33% — historically contraversial dosing with food requirement). Half-life ~36 h. Gefitinib: ~60% bioavailability (no significant food effect), half-life ~48 h.

## Clinical Efficacy

Multiple head-to-head trials (IPASS, ENSURE, others) show equivalent efficacy in EGFR-mutated NSCLC. Both reduce HbA1c/tumor response rate ~70–75% in EGFR-mutated patients.

## Unique Erlotinib Indications

Erlotinib is FDA-approved for pancreatic cancer (with gemcitabine) — the only EGFR TKI with this indication. This was a modest overall survival benefit (~2 weeks) in EGFR-unselected pancreatic cancer.

## Key Takeaways

- Both 1st-gen reversible EGFR TKIs; largely interchangeable for NSCLC
- Erlotinib: unique pancreatic cancer indication
- Both now second-choice behind osimertinib for NSCLC