Erlotinib vs Afatinib

## Overview

Erlotinib (1st-gen, reversible) and afatinib (2nd-gen, irreversible pan-ErbB) differ in binding mechanism and spectrum. Head-to-head LUX-Lung 8 showed afatinib superior to erlotinib in squamous NSCLC with EGFR expression.

## Mechanism of Action

Erlotinib: reversible ATP-competitive EGFR inhibitor. Afatinib: irreversible pan-ErbB inhibitor (EGFR, HER2, HER4).

## Clinical Evidence

LUX-Lung 7 (afatinib vs gefitinib in EGFR-mutated NSCLC): afatinib superior PFS and time-to-treatment failure. LUX-Lung 8 (afatinib vs erlotinib in 2nd-line squamous NSCLC): afatinib superior PFS and OS.

## Toxicity Profile

Afatinib's pan-ErbB inhibition causes more diarrhea, rash, and mucositis vs. erlotinib. Both require dose adjustments for Grade 2+ toxicity.

## Key Takeaways

- Afatinib: superior to erlotinib in head-to-head trials (LUX-Lung 7, 8)
- Erlotinib: unique pancreatic cancer indication; simpler toxicity profile
- Both now second-line options behind osimertinib for EGFR-mutated NSCLC