dacomitinib

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]