Lung Cancer: Dacomitinib

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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.

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Combining Biomarkers for Immunotherapy
Published OnlineFirst October 30, 2018; DOI: 10.1158/2159-8290.CD-NB2018-143 NEWS IN BRIEF also showed that it could be applicable Dacomitinib Approved, to CD22-targeted CAR T-cell therapy. “What’s really interesting is that but Might Not Be Used they uncovered a gene transfer–related The FDA approved the EGFR inhibi- mechanism of relapse, which I don’t tor dacomitinib (Vizimpro; Pfizer) as a think has been seen before,” says first-line therapy for patients with meta- Marcela Maus, MD, PhD, of Massachu- static, EGFR-mutant non–small cell setts General Hospital Cancer Center lung cancer (NSCLC). Clinicians, how- Structural formula for dacomitinib. in Boston. Inadvertent CAR19 trans- ever, doubt that the drug will be used duction aside, she notes, this single much in clinical practice, as it joins a treating brain metastases (J Clin Oncol B cell likely possessed additional char- crowded field of EGFR inhibitors that 2018 Aug 28 [Epub ahead of print]). acteristics that enabled it to survive includes osimertinib (Tagrisso; Astra- “I still think that osimertinib remains the therapy manufacturing process, Zeneca), the current standard of care. the standard for first-line [therapy] because engineered T cells are typically Instead, they are focused on the next based on toxicity, and based on its quick to eliminate any leukemic cells wave of therapeutic options. ability to elicit meaningful responses in in the patient-derived product. Dacomitinib was approved based on patients with brain metastasis,” he says. Ruella agrees that “some combina-
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