Dacomitinib Prolongs Progression-Free Survival vs Gefitinib in First-Line Treatment of EGFR-Mutant NSCLC

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“Dacomitinib treatment was superior to gefitinib … in the first-line treatment of patients with EGFR mutation–positive NSCLC and should be considered as a new treatment option for this population.”
— Yi-Long Wu, MD

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THE PHASE III ARCHER 1050 trial has shown superior progression-free survival with the second-generation irreversible epidermal growth factor receptor (EGFR) tyrosine kinase inhibitor dacomitinib vs gefitinib (Iressa) in the first-line treatment of advanced EGFR-mutant non–small-cell lung cancer (NSCLC) in a mostly Asian population. The study was reported by Yi-Long Wu, MD, of Guangdong Lung Cancer Institute, Guangdong General Hospital, and colleagues in The Lancet Oncology.1 

Study Details 

IN THE OPEN-LABEL trial, 452 adult patients with newly diagnosed disease and 1 EGFR mutation (exon 19 deletion or Leu858Arg) from 71 sites in China, Hong Kong, Japan, South Korea, Poland, Italy, and Spain were randomized between May 2013 and March 2015 to receive oral dacomitinib at 45 mg/d (n = 277) or oral gefitinib at 250 mg/d (n = 255) in 28-day cycles until disease progression or treatment discontinuation for other reasons. Randomization was stratified by race and EGFR mutation type. The primary endpoint was progression-free survival on a masked independent review in the intention-to-treat population. 

In the dacomitinib vs gefitinib groups: median age was 62 vs 61 years (41% vs 38% ≥ 65 years); 64% vs 56% were female; 75% vs 78% of patients were Asian and 25% vs 22% were white; Eastern Cooperative Oncology Group performance status was 0 for 33% vs 28% and 1 for 67% vs 72%; disease stage at screening was IIIB in 8% vs 7% and IV in 81% vs 81% (unknown in remainder); smoking status was never for 65% vs 64%, former for 29% vs 28%, and current for 7% vs 8%; and 59% in both had exon 19 deletion and 41% in both had Leu858Arg mutation. 

Progression-Free Survival 

MEDIAN DURATION of follow-up for progression-free survival was 22.1 months. Median progression-free survival was 14.7 months (95% confidence interval [CI] = 11.1–16.6) months in the dacomitinib group vs 9.2 months (95% CI = 9.1–11.0 months) in the gefitinib group (hazard ratio [HR] = 0.59, P < .0001). Estimated progression-free survival at 24 months was 30.6% vs 9.6%. On investigator assessment, median progression-free survival was 16.6 vs 11.0 months (HR = 0.62, P < .0001). 

In a subgroup analysis based on a masked independent review, progression-free survival hazard ratios were 0.51 (95% CI = 0.39– 0.66) among Asian patients and 0.89 (95% CI = 0.57–1.39) among non-Asian patients. Hazard ratios were 0.55 (95% CI = 0.41–0.75) among those with exon 19 deletion and 0.63 (95% CI = 0.44–0.88) among those with Leu858Arg; 0.72 (95% CI = 0.51–1.02) among males and 0.50 (95% CI = 0.37–0.67) among females; and 0.51 (95% CI = 0.39–0.68) among never smokers and 0.72 (95% CI = 0.49–1.05) among former or current smokers. 

An objective response occurred in 75% vs 72% of patients (P = .423), with a median response duration of 14.8 vs 8.3 months (P < .0001). Response rates were 76% vs 70% among patients with exon 19 deletion, 73% vs 74% among those with Leu858Arg mutation, and 75% among Asian patients and 68% among non-Asian patients. 

Overall survival data were not mature; at data cutoff for the progression-free survival analysis, death had occurred in 33% vs 40% of patients. Postprogression systemic treatment was received by 41% of the dacomitinib group and 56% of the gefitinib group, with the most common in both groups being pemetrexed (Alimta), carboplatin, cisplatin, and osimertinib (Tagrisso). 

Adverse Events 

THE MOST COMMON adverse events of any grade were diarrhea (87%), paronychia (62%), dermatitis acneiform (49%), and stomatitis (44%) in the dacomitinib group and diarrhea (56%), alanine transaminase (ALT) increase (39%), and aspartate transaminase (AST) increase (36%) in the gefitinib group. Grade 3 or 4 adverse events occurred in 53% (grade 3 in 51%) vs 32% (grade 3 in 30%); the most common adverse events in the dacomitinib group were dermatitis acneiform (14% vs 0%), diarrhea (8% vs 1%), and paronychia (7% vs 1%), and the most common adverse event in the gefitinib group was an elevated ALT level (8% vs 1%). 

Treatment-related serious adverse events occurred in 9% vs 4%, with the most common in the dacomitinib group being gastrointestinal disorders (4%). Treatment-related adverse events led to death in two patients in the dacomitinib group (due to untreated diarrhea in one and untreated cholelithiasis/liver disease in one) and in one patient in the gefitinib group (due to sigmoid colon diverticulitis/rupture complicated by pneumonia). 

The investigators concluded: “Dacomitinib treatment was superior to gefitinib with respect to progression-free survival and duration of response in the first-line treatment of patients with EGFR mutation–positive NSCLC and should be considered as a new treatment option for this population.” ■

DISCLOSURE: The study was funded by SFJ Pharmaceuticals Group and Pfizer. For full disclosures of the study authors, visit 


1. Wu YL, Cheng Y, Zhou X, et al: Dacomitinib versus gefitinib as first-line treatment for patients with EGFR-mutation-positive non-small-cell lung cancer (ARCHER 1050): A randomised, open-label, phase 3 trial. Lancet Oncol. September 25, 2017 (early release online).

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