Vizimpro (Dacomitinib) Receives EU Approval as First-Line Treatment for EGFR-Mutated NSCLC
Apr 04, 2019 16:25
CST Updated
16:25
Pfizer
Pharmaceutical R&D Developer
European Medicines Agency
The European Medicines Agency (EMA) is a decentralized agency of the European Union (EU), located in London. It began operations in 1995. The agency is responsible for the scientific evaluation, supervision, and safety monitoring of medicines developed by pharmaceutical companies for use in the EU. By ensuring that all medicines available on the EU market are safe, effective, and of high quality, the EMA protects public and animal health in the 28 EU Member States and countries of the European Economic Area.
April 04, 2019 /BioValleyBIOON/ -- US pharmaceutical giantPfizerPfizer recently announced that the European Commission (EC) has approved its second-generation EGFR-targeted drug Vizimpro (dacomitinib, 45 mg) as a monotherapy for the first-line treatment of adult patients with locally advanced or metastatic non-small cell lung cancer (NSCLC) harboring activating epidermal growth factor receptor (EGFR) mutations.
Vizimpro also marks the latest achievement in Pfizer’s commitment to advancing precision medicine development and improving outcomes for patients with mutation-driven lung cancer. Currently, Pfizer has developed three targeted therapies for three distinct types of mutation-driven lung cancer: the first-generation ALK inhibitor Xalkori (crizotinib) for the treatment of ALK-positive or ROS1-positive non-small cell lung cancer (NSCLC); the third-generation ALK inhibitor Lorbrena (lorlatinib) for the treatment of ALK-positive NSCLC; and the second-generation EGFR inhibitor Vizimpro for the treatment of EGFR-mutated NSCLC.
Vizimpro is an oral, once-daily, irreversible pan-human epidermal growth factor receptor (pan-EGFR) tyrosine kinase inhibitor (TKI). In the United States, Vizimpro was approved by the FDA in late September 2018 for use in patients who have undergoneFDAApproved for the first-line treatment of patients with metastatic NSCLC confirmed by an approved test kit to have epidermal growth factor receptor (EGFR) exon 19 deletions or exon 21 L858R substitution mutations. Vizimpro has also been approved by Japanese regulatory authorities for patients with EGFR mutation-positive, unresectable or recurrent NSCLC.
The approval of Vizimpro was based on data from the Phase III clinical study ARCHER 1050. This study was a randomized, open-label, head-to-head Phase III trial conducted in patients with locally advanced or metastatic NSCLC harboring EGFR-activating mutations, evaluating Vizimpro versusAstraZenecaEfficacy and Safety of the First-Generation EGFR-Targeted Drug Iressa (Iressa, Generic Name: Gefitinib) in First-Line Treatment. The Primary Endpoint Was Progression-Free Survival (PFS), and the Secondary Endpoint Was Overall Survival (OS).
Study data showed that, compared with the Iressa treatment group, the Vizimpro treatment group achieved a statistically significant and clinically meaningful prolongation of progression-free survival (PFS) (median PFS: 14.7 months vs. 9.2 months), with a 41% significant reduction in the risk of death or disease progression (HR=0.59 [95% CI=0.47-0.74], p<0.0001), thereby meeting the primary endpoint of the study. Last June, at the American Society of Clinical OncologyTumorSociety AnnualMeeting(ASCO 2018) The OS data presented showed that the median OS in the Vizimpro treatment group was 34.1 months (95% CI: 29.5–37.7), which was 7 months longer than that in the Iressa treatment group (median OS: 26.8 months [95% CI: 23.7–32.1]). At month 30 of treatment, the survival rate was 56.2% in the Vizimpro group and 46.3% in the Iressa group. Subgroup analyses across most baseline characteristics were consistent with the primary OS analysis results, including in patients with common exon 19 and exon 20 submutations.
In terms of safety, the most common adverse reactions (≥20%) in the Vizimpro treatment group included: diarrhea (87%), rash (69%), paronychia (64%), stomatitis (45%), decreased appetite (31%), dry skin (30%), weight loss (26%), alopecia (23%), cough (21%), and pruritus (21%). Serious adverse reactions occurred in 27% of patients in the Vizimpro treatment group, with the most common (≥1%) seriousAdverse Reactionswere diarrhea (2.2%) and interstitial lung disease (1.3%).
In recent years, despite significant advances in the clinical treatment of patients with non-small cell lung cancer (NSCLC) harboring EGFR-activating mutations, the disease remains highly challenging, with an urgent need for new therapeutic options. Overall survival (OS) data from pivotal head-to-head Phase III studies are highly encouraging, demonstrating that the median OS for patients with EGFR-activating mutation-positive NSCLC treated with Vizimpro approaches three years, representing a significant improvement compared to Iressa, the current first-line standard-of-care therapy.
Hospital of Romagna, ItalyTumorand Federico C, Director of the Department of HematologyappUzzo stated, “Over the past 20 years,Biomarker“Driver-directed therapy has become the standard of care for patients with EGFR-mutant NSCLC. In the ARCHER 1050 study, Vizimpo demonstrated a highly impressive improvement in progression-free survival compared to first-generation standard-of-care agents, and I am pleased that this medication will now be available to patients with NSCLC in Europe.”
PfizerTumorDr. Andreas Penk, President of International Developed Markets, stated, “Lung cancer remains the leading cause of cancer-related deaths worldwide. Despite advances in biomarker-driven therapies, overcoming resistance remains key to treating EGFR-mutated NSCLC. Compared with existing therapies in Phase III studies, Vizimpro improved progression-free survival by more than five months. This drug will provide a new option for patients with EGFR-mutated NSCLC and reinforce Pfizer’s ongoing commitment to addressing unmet medical needs among patients in Europe.”(BioValley Bioon.com)