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Dacomitinib Approaches EU Approval for EGFR+ NSCLC

Jason M. Broderick @jasoncology
Published: Friday, Feb 01, 2019

Chris Boshoff, MD, PhD
Chris Boshoff, MD, PhD
The European Medicines Agency’s Committee for Medicinal Products for Human Use (CHMP) has recommended approval of dacomitinib (Vizimpro) for the frontline treatment of adult patients with metastatic non–small cell lung cancer (NSCLC) with EGFR-activating mutations, according to Pfizer, the manufacturer of the pan-human EGFR TKI.

The CHMP recommendation was based on findings from the phase III ARCHER 1050 trial, in which dacomitinib reduced the risk of disease progression or death by more than 40% and resulted in an average 6.5-month improvement in response duration compared with gefitinib (Iressa) as a first-line treatment for patients with advanced, EGFR-positive NSCLC.

The median progression-free survival (PFS) for patients who received dacomitinib was 14.7 months compared with 9.2 months for participants who received gefitinib (HR, 0.59; 95% CI, 0.47-0.74; P <.0001). The median duration of response (DOR) was 14.8 months with dacomitinib versus 8.3 months with gefitinib (HR, 0.40; 95% CI, 0.31-0.53; P <.0001).1

Data presented at the 2018 ASCO Annual Meeting also showed that at a median follow-up of 31.1 months, the median overall survival was 34.1 months in patients randomized to dacomitinib versus 26.8 months in those randomized to gefitinib.2

The European Commission will now review the CHMP recommendation and make a final decision on whether to approve dacomitinib for use in the European Union.

“Patients with EGFR-mutated non–small cell lung cancer, a disease that is associated with low overall survival rates, are in need of more treatment options. This positive CHMP opinion is an important step toward bringing this treatment to patients in Europe as a potential new first-line treatment option,” Chris Boshoff, MD, PhD, Chief Development Officer, Oncology, Pfizer Global Product Development, said in a press release.

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

A total of 452 patients were randomized in a 1:1 ratio to either receive 45 mg daily of dacomitinib (n = 227) or 250 mg daily of gefitinib (n = 225). Baseline patient characteristics were balanced across the 2 arms of the study, including in terms of race and smoking status. In the dacomitinib arm, about 75% of participants were Asian and nearly 65% were never-smokers. In the gefitinib arm, 78% were Asian and 64% were never-smokers. The median age was 61 to 62 years.

Although PFS was similar in both arms at the 6-month mark, the difference in PFS became very apparent by the 24-month mark. At 24 months, 30.6% of patients in the dacomitinib arm were progression free, compared with 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 arm (P <.3883). Overall survival data were not yet mature at the time of the analysis.

The data cutoff for the OS analysis was February 17, 2017, with 220 (48.7%) deaths observed at that time. The hazard ratio for OS was 0.76 (P = .0438) in favor of dacomitinib. The OS probability at 30 months was 56.2% in the dacomitinib arm and 46.3% in the gefitinib arm. One patient randomized to dacomitinib and 11 randomized to gefitinib had CNS metastases at progression.

OS subgroup analyses were consistent with the primary OS analysis across most baseline characteristics. Patients with exon 19 deletion had a median OS of 34.1 months with dacomitinib versus not reached with gefitinib (HR, 0.880 favoring dacomitinib; 95% CI, 0.613-1.262, P =.486). Those with exon 21 L858R mutation had a median OS of 32.5 months in the dacomitinib arm compared with 23 months in the gefitinib (HR, 0.71; 95% CI, 0.478-1.045; P =.0805).

In terms of adverse events (AEs), there was more toxicity observed in the dacomitinib arm than in the gefitinib arm. Gastrointestinal all-grade AEs were more common in the dacomitinib arm compared with the gefitinib arm, including diarrhea (87.2% vs 55.8%, respectively) and decreased appetite (30.8% vs 24.6%). More patients in the dacomitinib arm 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%). However, increases in ALT levels were observed more in the gefitinib arm (39.3%) compared with the dacomitinib arm (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. Discontinuation due to treatment-related AEs occurred in 10% versus 7% of the dacomitinib versus gefitinib arms, respectively.

Based on the ARCHER 1050 trial, the FDA approved dacomitinib in September 2018 for the frontline treatment of patients with metastatic NSCLC with EGFR exon 19 deletion or exon 21 L858R substitution mutations.


  1. 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).
  2. Mok T, Cheng Y, Zhou X, et al. Improvement in overall survival in a randomized study comparing dacomitinib with gefitinib in patients with advanced non-small cell lung cancer harboring EGFR-activating mutations. J Clin Oncol. 2018;36(suppl; abstr 9004).


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