Dacomitinib, a second-generation irreversible epidermal growth factor receptor tyrosine kinase inhibitor (EGFR-TKI) to treat non-small cell lung cancer

摘要

Dacomitinib (PF-00299804, Vizimpro) was developed as a second-generation, oral, irreversible inhibitor of human epidermal growth factor receptor (EGFR)1, -2 and -4 tyrosine kinase. On September 27, 2018, the United States Food and Drug Administration (FDA) approved dacomitinib for the first-line treatment of patients with metastatic non-small cell lung cancer (NSCLC) with EGFR exon 19 deletion or exon 21 L858R substitution mutations. On January 8, 2019, the Ministry of Health, Labour and Welfare of Japan approved this second-generation EGFR tyrosine kinase inhibitor (TKI) for the treatment of EGFR mutation-positive inoperable or recurrent NSCLC. The European Commission also approved dacomitinib on April 3, 2019, as monotherapy for the first-line treatment of adult patients with locally advanced or metastatic NSCLC with EGFR activating mutations. Approval of dacomitinib was based on a randomized, multicenter, open-label, active-controlled trial (ARCHER 1050; ClinicalTrials.gov Identifier NCT01774721) which demonstrated the safety and efficacy of dacomitinib compared to gefitinib in 452 patients with unresectable and metastatic NSCLC. Dacomitinib represents a powerful new treatment option compared with first-generation EGFR-TKIs. In this paper, we review the clinical and preclinical studies of dacomitinib and discuss the drug's clinical value.