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afatinib

Tuesday 10 June 2014

Gilotrif, Giotrif, Tomtovok, Tovok

WKP

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.

Targeted therapy

- 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.

Open references

- Dacomitinib in lung cancer: a "lost generation" EGFR tyrosine-kinase inhibitor from a bygone era? Drug Des Devel Ther. 2015 Oct 15;9:5641-53. doi : 10.2147/DDDT.S52787 PMID 26508839 [Free]