Comprehensive Monograph: Afatinib (DB08916)

Executive Summary

Afatinib is a second-generation, orally administered, irreversible tyrosine kinase inhibitor (TKI) belonging to the ErbB family blocker class of antineoplastic agents. Developed by Boehringer Ingelheim and marketed under brand names including Gilotrif and Giotrif, it represents a significant milestone in the targeted therapy of cancer.[1] Its primary clinical application is in the treatment of metastatic non-small cell lung cancer (NSCLC).[1] Specifically, it is indicated as a first-line treatment for patients whose tumors harbor non-resistant epidermal growth factor receptor (EGFR) mutations and as a second-line treatment for patients with metastatic squamous NSCLC that has progressed following platinum-based chemotherapy.[4]

The pharmacological distinction of Afatinib lies in its mechanism of action. Unlike first-generation reversible TKIs, Afatinib forms a covalent bond with the kinase domains of EGFR (ErbB1), human epidermal growth factor receptor 2 (HER2/ErbB2), and HER4 (ErbB4). This irreversible binding results in a potent, sustained, and broad-spectrum blockade of signaling pathways critical for tumor cell proliferation, survival, and differentiation.[6] This mechanism confers activity not only against common activating EGFR mutations but also against certain mutations that are resistant to first-generation agents.[1]