On April 4, 2018 Pfizer Inc. reported 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 (TKI), for the first-line treatment of patients with locally advanced or metastatic non-small cell lung cancer (NSCLC) with EGFR-activating mutations (Press release, Pfizer, APR 4, 2018, View Source [SID1234525178]). The European Medicines Agency has also accepted the Marketing Authorization Application for dacomitinib for the same indication.
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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 (PDUFA) goal date for a decision by the FDA is in September 2018.
"While significant progress has been made in the treatment of patients with non-small cell lung cancers harboring EGFR-activating mutations, it remains a challenging disease and new treatment options are needed," said Mace Rothenberg, M.D., 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, 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 non-small cell lung cancer."
Dacomitinib is the second investigational Pfizer lung cancer medicine to receive regulatory acceptance within two months, reinforcing Pfizer’s commitment to patients with NSCLC where there continues to be a significant unmet need.
The submissions are based on results from the Phase 3 ARCHER 1050 study, a global head-to-head trial investigating dacomitinib (n=227) compared to 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 (PFS) of 14.7 months compared with 9.2 months in patients treated with gefitinib, as measured by Blinded Independent Central Review (BICR). This difference represented a 41 percent reduction in the risk of disease progression or death for patients treated with dacomitinib compared with gefitinib (HR = 0.59 [95% CI: 0.47,0.74], p <0.0001) as a first-line treatment in locally advanced or metastatic NSCLC with EGFR-activating mutations.
The adverse events (AEs) observed with dacomitinib in the study were consistent with findings from previous trials. The most common AEs were diarrhea (87%), nail changes (62%), rash/dermatitis acneiform (49%), and mouth sores (44%). The most common Grade 3 AEs with dacomitinib were rash (14%) and diarrhea (8%). Grade 4 AEs occurred in 2 percent 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 AEs for dacomitinib was 10 percent compared to 7 percent for gefitinib.
The ARCHER 1050 results were published in Lancet Oncology, shared as an oral late-breaker presentation at the 2017 American Society of Clinical Oncology (ASCO) (Free ASCO Whitepaper) Annual Meeting and featured in the ASCO (Free ASCO Whitepaper) press program. A final assessment of overall survival from ARCHER 1050 will be presented at a medical meeting later this year.
About Dacomitinib
Dacomitinib is an investigational, oral, once-daily, irreversible pan-human epidermal growth factor receptor tyrosine kinase inhibitor (TKI). It has not received regulatory approval in any country.
In 2012, Pfizer and SFJ Pharmaceuticals Group entered into a collaborative development agreement to conduct ARCHER 1050 across multiple sites.
About Non-Small Cell Lung Cancer
Lung cancer is the leading cause of cancer deaths worldwide.1 NSCLC accounts for about 85 percent of lung cancer cases and remains difficult to treat, particularly in the metastatic setting.2 Approximately 75 percent of NSCLC patients are diagnosed late with metastatic or advanced disease where the five-year survival rate is only five percent.2,3,4
EGFR is a protein that helps cells grow and divide. When the EGFR protein is mutated it can cause cancer cells to form. EGFR mutations occur in 10 to 35 percent of NSCLC tumors globally, yet the disease is associated with low survival rates and disease progression remains a challenge. 5,6
About Pfizer in Lung Cancer
Pfizer Oncology is committed to addressing the unmet needs of patients with lung cancer, the leading cause of cancer-related deaths worldwide and a particularly difficult-to-treat disease. Pfizer strives to address the diverse and evolving needs of patients with non-small cell lung cancer (NSCLC) by developing efficacious and tolerable therapies, including biomarker-driven therapies and immuno-oncology (IO) agents and combinations. By combining leading scientific insights with a patient-centric approach, Pfizer is continually advancing its work to match the right patient with the right medicine at the right time. Through our growing research pipeline and collaboration efforts, we are committed to delivering renewed hope to patients living with NSCLC.