RESEARCH HIGHLIGHTS Nature Reviews Clinical Oncology 12, 3 (2015); published online 25 November 2014; doi:10.1038/nclinonc.2014.210 LUNG CANCER Dacomitinib: getting on target after negative ARCHER trial Despite the progress made in treating setting did not demonstrate any outcome To establish whether dacomitinib patients with non-small-cell lung cancer advantage for dacomitinib. However, the represents a new treatment advance in (NSCLC) with standard-of-care EGFR role of dacomitinib in the first-line setting patients with advanced-stage EGFR-mutant tyrosine kinase inhibitors (TKI), such as in patients with activating EGFR mutations NSCLC, this drug needs to be compared gefitinib, in the first-line setting, it is well has not been investigated. directly with a first-line agent; in this regard, known that patients inevitably develop Pasi Jänne and coauthors now reveal a phase III trial comparing dacomitinib with drug resistance within 1 year and relapse. encouraging data from a multicentre, gefitinib as initial therapy for patients Hence, new therapeutic approaches are phase II trial that assessed dacomitinib with advanced-stage disease in ongoing. desperately needed. (30 mg or 45 mg) in 89 patients with Dacomitinib is a pan-HER inhibitor advanced-stage NSCLC (45 had EGFR Lisa Hutchinson that targets EGFR, HER2 and HER4, and mutations). Patients with known KRAS has shown promising preclinical activity. mutations or known EGFR wild-type Original article Jänne, P. et al. Dacomitinib as first-line As is often the case, targeted agents do not disease and nonadenocarcinoma disease treatment in patients with clinically or molecularly selected provide survival advantages in unselected were excluded. Progression-free survival advanced non-small-cell lung cancer: a multicentre, patient populations. Indeed, although (PFS), the primary end point of the study, open‑label, phase 2 trial. Lancet Oncol. doi:10.1016/ S1470-2045(14)70461-9 phase II data with dacomitinib provided was 76.8% at 4 months in the enrolled Further reading Ramalingam, S. S. et al. Dacomitinib positive outcomes in unselected patients population and 95.5% in patients with versus erlotinib in patients with advanced-stage, previously with NSCLC, the subsequent phase III an EGFR mutation. The most common treated non-small-cell lung cancer (ARCHER 1009): ARCHER trial that compared erlotinib adverse events were diarrhoea, dermatitis a randomised, double-blind, phase 3 trial. Lancet Oncol. 15, 1369–1378 (2014) versus dacomitinib in the second-line acneiform, dry skin, and stomatitis. NATURE REVIEWS | CLINICAL ONCOLOGY VOLUME 12 | JANUARY 2015 © 2015 Macmillan Publishers Limited. All rights reserved.