Priority Review Granted by FDA to Dacomitinib for Frontline Treatment in NSCLC

According to Pfizer, manufacturer of a pan-human EGFR tyrosine kinase inhibitor (TKI), a priority review has been granted by the FDA for their TKI inhibitor, dacomitinib, in the frontline setting for patients with&nbsp;<em>EGFR</em>-positive locally advanced or metastatic non&ndash;small cell lung cancer.

According to Pfizer, manufacturer of a pan-human EGFR tyrosine kinase inhibitor (TKI), a priority review has been granted by the FDA for their TKI inhibitor, dacomitinib, in the frontline setting for patients withEGFR-positive locally advanced or metastatic non—small cell lung cancer (NSCLC).

Based on the results from the phase III ARCHER 1050 trial, this application is submitted after findings demonstrated reduced risk of disease progression or death by more than 40% with treatment of dacomitinib, resulting in an average of 6.5 month improvement in response duration. These results are compared to gefitinib (Iressa) as a frontline option for patients with advanced, EGRF-positive NSCLC.

For patients who received dacomitinib, median progression-free survival (PFS) was 14.7 months versus 9.2 months for participants who received gefitinib (HR, 0.59; 95% CI, 0.47-0.74; P<.0001). Median duration of response (DOR) was 14.8 months in the dacomitinib group compared to 8.3 months in the gefitinib group (HR, 0.40; 95% CI, 0.31-0.53; P<.0001).

Priority designation is expected to expedite the development and review of dacomitinib for this patient population. The FDA is scheduled to make a decision by September 2018. The European Medicines Agency has also accepted the Marketing Authorization Application for dacomitinib for the same indication, according to Pfizer.

“While significant progress has been made in the treatment of patients with non—small cell lung cancers harboringEGFR-activating mutations, it remains a challenging disease and new treatment options are needed,” said Mace Rothenberg, MD, chief development officer in Oncology at 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,” he added. “These filing acceptances are an important step toward increasing treatment options for patients with locally advanced or metastaticEGFR-mutated non—small cell lung cancer.”

Designed with a primary endpoint of PFS, ARCHER 1050 was assessed by blinded independent review with secondary endpoints of DOR, overall response rate (ORR), and safety. Patients with newly diagnosed stage IIIB/IV, EGFR-positive NSCLC who had not received a previous systemic therapy including TKIs and an ECOG performance status of 0 or 1 were enrolled for this study. Also, patients could not have any metastases in the central nervous system (CNS).

Randomized to a 1:1 ratio, 452 patients were separated into 2 groups: 227 to receive 45 mg daily of dacomitinib and 225 patients to receive 250 mg daily of gefitinib. Characteristics of patients at baseline were balanced amongst the 2 groups, in terms of race and smoking status.

About 75% of participants were Asian and nearly 65% were never-smokers in the dacomitinib group. Of patients in the gefitinib group, 78% were Asian and 64% were never-smokers. Median age between both groups was 61 to 62 years.

The difference in PFS became very obvious at the 24-month mark. At 24 months, 30.6% of patients in the dacomitinib group were progression free, versus 9.6% in the gefitinib group. However, there was not a statistically significant difference in ORR, with 74.9% of patients in the dacomitinib achieving a response versus 71.6% of patients in the gefitinib group (P<.3883). Data for overall survival was not ready at the time of analysis.

More toxicity was observed in the dacomitinib arm than in the gefitinib arm, in terms of adverse events (AEs). The most common QE in the dacomitinib group was gastrointestinal all-grade versus the gefitinib group, including diarrhea (87.2% vs 55.8%, respectively) and decreased appetite (30.8% vs 24.6%). In the dacomitinib group, more patients compared with the gefitinib arm also experienced paronychia (61.7% vs 20.1%), dermatitis acneiform (48.9% vs 28.6%), and stomatitis (43.6% vs 17.9%). Increases in ALT levels were also observed more often in the gefitinib group (39.3%) versus the dacomitinib group (19.4%).

The most frequent grade 3 AEs in the dacomitinib arm were rash (14%) and diarrhea (8%). Two percent of patients receiving dacomitinib had grade 4 AEs. There were two grade 5 AEs, diarrhea and liver disease. AE-related discontinuation occurred in 10% in the dacomitinib group versus 7% in the gefitinib group.


Mok T, Cheng Y, Zhou X, et al. Dacomitinib versus gefitinib for the first-line treatment of advanced EGFR mutation positive non-small cell lung cancer (ARCHER 1050): a randomized, open-label phase 3 trial. J Clin Oncol. 2017;35(suppl; abstr LBA9007).