DACOMITINIB FIRST LINE FOR EGFRm NSCLC

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). These results were reported by Wu et al in The Lancet Oncology.

Study Details

In the open-label trial, 452 adult patients (aged ≥ 20 years) with newly diagnosed disease and 1 EGFRmutation (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 masked independent review in the intention-to-treat population. In the dacomitinib and gefitinib groups, 75% vs 78% of patients were Asian, and 25% vs 22% were white; 59% in both groups had exon 19 deletion, and 41% in both groups had Leu858Arg.

Progression-Free Survival

The 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%. In a subgroup analysis, hazard ratios were 0.51 (95% CI = 0·39–0.66) among Asian patients, 0.89 (95% CI = 0.57–1.39) among non-Asian patients, 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.

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). Overall survival data were not mature; at data cutoff for the progression-free survival analysis, death had occurred in 33% vs 40% of patients.

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 increase (36%) in the gefitinib group. The most common grade 3 or 4 adverse events were dermatitis acneiform (14% vs 0%), diarrhea (8% vs 1%), and elevated ALT (1% vs 8%). Treatment-related serious adverse events occurred in 9% vs 4%. Treatment-related adverse events led to death in two patients in the dacomitinib group and in one patient in the gefitinib group.

The investigators concluded: “Dacomitinib significantly improved progression-free survival over gefitinib in first-line treatment of patients with EGFR-mutation-positive NSCLC and should be considered as a new treatment option for this population.”

The study was funded by SFJ Pharmaceuticals Group and Pfizer.

Yi-Long Wu, MD, of Guangdong General Hospital and Guangdong Academy of Medical Sciences, is the corresponding author of The Lancet Oncology article.