Despite the progress made in treating patients with non-small-cell lung cancer (NSCLC) with standard-of-care EGFR tyrosine kinase inhibitors (TKI), such as gefitinib, in the first-line setting, it is well known that patients inevitably develop drug resistance within 1 year and relapse. Hence, new therapeutic approaches are desperately needed.

Dacomitinib is a pan-HER inhibitor that targets EGFR, HER2 and HER4, and has shown promising preclinical activity. As is often the case, targeted agents do not provide survival advantages in unselected patient populations. Indeed, although phase II data with dacomitinib provided positive outcomes in unselected patients with NSCLC, the subsequent phase III ARCHER trial that compared erlotinib versus dacomitinib in the second-line setting did not demonstrate any outcome advantage for dacomitinib. However, the role of dacomitinib in the first-line setting in patients with activating EGFR mutations has not been investigated.

Pasi Jänne and coauthors now reveal encouraging data from a multicentre, phase II trial that assessed dacomitinib (30 mg or 45 mg) in 89 patients with advanced-stage NSCLC (45 had EGFR mutations). Patients with known KRAS mutations or known EGFR wild-type disease and nonadenocarcinoma disease were excluded. Progression-free survival (PFS), the primary end point of the study, was 76.8% at 4 months in the enrolled population and 95.5% in patients with an EGFR mutation. The most common adverse events were diarrhoea, dermatitis acneiform, dry skin, and stomatitis.

To establish whether dacomitinib represents a new treatment advance in patients with advanced-stage EGFR-mutant NSCLC, this drug needs to be compared directly with a first-line agent; in this regard, a phase III trial comparing dacomitinib with gefitinib as initial therapy for patients with advanced-stage disease in ongoing.