FDA and EMA Accept Regulatory Submissions for Dacomitinib in Metastatic NSCLC With EGFR-Activating Mutations

On April 4, Pfizer Inc announced that the U.S. Food and Drug Administration (FDA) accepted the company’s new drug application and granted Priority Review for dacomitinib, a pan-human epidermal growth factor receptor (EGFR) tyrosine kinase inhibitor, for the first-line treatment of patients with locally advanced or metastatic non­–small cell lung cancer (NSCLC) with EGFR-activating mutations. The European Medicines Agency (EMA) has also accepted a marketing authorization application for dacomitinib for the same indication.

The FDA grants Priority Review to medicines that may offer significant advances in treatment or may provide a treatment where no adequate therapy exists. The Prescription Drug User Fee Act goal date for a decision by the FDA is September 2018.

“While significant progress has been made in the treatment of patients with NSCLC harboring EGFR-activating mutations, it remains a challenging disease, and new treatment options are needed,” said Mace Rothenberg, MD, Chief Development Officer, Oncology, Pfizer Global Product Development. “In the pivotal clinical trial that supports these applications, dacomitinib showed clinically meaningful improvement in progression-free survival over gefitinib [Iressa], one of the first EGFR-targeted therapies to demonstrate activity in this disease. These filing acceptances are an important step toward increasing treatment options for patients with locally advanced or metastatic EGFR-mutated NSCLC.”


The submissions are based on results from the phase III ARCHER 1050 study, a global head-to-head trial comparing dacomitinib (n = 227) vs gefitinib (n = 225) that showed dacomitinib may offer a clinically meaningful improvement over gefitinib. Patients that received dacomitinib in the study experienced a median progression-free survival of 14.7 months compared with 9.2 months in patients treated with gefitinib, as measured by blinded independent central review. This difference represented a 41% reduction in the risk of disease progression or death for patients treated with dacomitinib compared with gefitinib (hazard ratio = 0.59, 95% confidence interval = 0.47–0.74, P < .0001) as a first-line treatment in locally advanced or metastatic NSCLC with EGFR-activating mutations.

The adverse events observed with dacomitinib in the study were consistent with findings from previous trials. The most common were diarrhea (87%), nail changes (62%), rash/dermatitis acneiform (49%), and mouth sores (44%). The most common grade 3 adverse events with dacomitinib were rash (14%) and diarrhea (8%). Grade 4 events occurred in 2% of dacomitinib-treated patients. There was one case of grade 5 diarrhea and one case of grade 5 liver disease. The discontinuation rate due to treatment-related adverse events for dacomitinib was 10%, compared to 7% for gefitinib.

The ARCHER 1050 results were published by Wu et al in The Lancet Oncology and shared as an oral late-breaking presentation by Mok et al at the 2017 ASCO Annual Meeting (LBA9007).

A final assessment of overall survival from ARCHER 1050 will be presented at a medical meeting later this year.

The content in this post has not been reviewed by the American Society of Clinical Oncology, Inc. (ASCO®) and does not necessarily reflect the ideas and opinions of ASCO®.




By continuing to browse this site you permit us and our partners to place identification cookies on your browser and agree to our use of cookies to identify you for marketing. Read our Privacy Policy to learn more.