Dacomitinib as first-line treatment for EGFR mutation-positive non-small cell lung cancer

ABSTRACT Introduction: Dacomitinib is a second-generation epidermal growth factor receptor tyrosine kinase inhibitor (EGFR TKI). Recent results from ARCHER 1050, the first randomized, open-label, Phase 3 trial of a second-generation vs. a first-generation EGFR TKI, showed that dacomitinib improves progression-free survival and overall survival compared with gefitinib as a first-line treatment in patients with EGFR mutation-positive advanced non-small cell lung cancer (NSCLC). Areas covered: We review the efficacy and safety of dacomitinib as a first-line treatment of EGFR mutation-positive NSCLC, including the management of toxicity, and evaluate the activity of dacomitinib against brain metastases. Additionally, the optimal treatment sequence given EGFR TKI choice, resistance mechanisms, activity against rare mutations, and real-world dosing is discussed. Expert opinion: The introduction of EGFR TKIs has changed the treatment strategy for patients with EGFR mutation-positive NSCLC. The second- and third-generation EGFR TKIs are the result of research elucidating mechanisms of resistance to first-generation EGFR TKIs. There is now more than one treatment option for patients with EGFR mutation-positive advanced NSCLC that improves survival, highlighting the need to more clearly understand the use of the right drug for the right person at the right time and how the appropriate treatment sequence may provide optimal outcomes for these patients.