Tuesday 10 June 2014
Gilotrif, Giotrif, Tomtovok, Tovok
Definition: Afatinib acts as an irreversible covalent inhibitor of the receptor tyrosine kinases epidermal growth factor receptor (EGFR) and erbB-2 (HER2).
Afatinib is a drug approved in United States, Europe, Taiwan, Mexico, Chile and Japan as well as other countries for the first-line treatment of patients with distinct types of metastatic (EGFR mutation positive) non-small cell lung carcinoma (NSCLC), developed by Boehringer Ingelheim.
non-small-cell lung cancer (NSCLC)
- EGFR tyrosine-kinase inhibitors (EGFR-TKIs or TKIs ) have now been firmly established as the first-line treatment for non-small-cell lung cancer (NSCLC) patients harboring activating EGFR mutations, based on several prospective randomized Phase III trials.
- However, despite significantly improved overall response rate and improved median progression-free survival when compared to platinum-doublet chemotherapy, EGFR-mutant NSCLC patients treated with EGFR TKIs invariably progress due to the emergence of acquired resistances, with the gatekeeper T790M mutation accounting for up to 60% of the resistance mechanisms.
- Second-generation irreversible EGFR TKIs were developed in part to inhibit the T790M mutation, in addition to the common activating EGFR mutations.
- Dacomitinib is one such second-generation EGFR TKI designed to inhibit both the wild-type (WT) EGFR and EGFR T790M.
- Afatinib is another second-generation EGR TKI that has been now been approved for the first-line treatment of EGFR-mutant NSCLC patients, while dacomitinib continues to undergo clinical evaluation.
- Given the rapid development of third-generation EGFR TKIs and the approval of gefitinib, erlotinib, and afatinib as first-line treatment of EGFR-mutant NSCLC patients, the future role of dacomitinib in the treatment of NSCLC seems to be limited.