afatinib

Afatinib is a small molecule tyrosine kinase inhibitor that irreversibly blocks the ErbB family of receptor tyrosine kinases, including EGFR (ErbB1), HER2 (ErbB2), and, to a lesser extent, HER4 (ErbB4). By covalently binding to these receptors, afatinib inhibits signaling pathways such as RAS-RAF-MEK-ERK and PI3K-AKT that promote tumor cell growth and survival. This mechanism makes it active against tumors driven by EGFR or HER2 signaling.

Indications and use are centered on non-small cell lung cancer (NSCLC). Afatinib is approved for adults with metastatic NSCLC whose tumors harbor activating EGFR mutations, such as exon 19 deletions or the L858R point mutation. It is used as first-line therapy for this mutational subset in various regulatory regions. Afatinib has also been studied in other EGFR- or HER2-driven cancers, but its approval is specific to EGFR-mutant metastatic NSCLC in routine practice.

Administration and dosing typically involve 40 mg taken once daily, orally. The dose may be adjusted for tolerability, with reductions to 20 mg or 30 mg as needed. The drug can be taken with or without food; tablets should be swallowed whole. Dose interruptions and discontinuation may occur for intolerable adverse effects or serious toxicity.

Common adverse effects include diarrhea, rash or acneiform dermatitis, stomatitis, paronychia, decreased appetite, and fatigue. Serious risks include interstitial lung disease, hepatotoxicity, and other severe dermatologic or hematologic toxicities. Monitoring typically includes regular clinical assessment and laboratory tests, with dose modifications guided by tolerance. Afatinib is not recommended in patients with significant baseline interstitial lung disease and should be used during pregnancy only if clearly needed.