No Progression-Free Survival Benefit of Dacomitinib vs Erlotinib Overall or in KRAS Wild-Type Disease in Pretreated Advanced NSCLC


Key Points

  • Dacomitinib was not associated with improved progression-free survival vs erlotinib among all patients or among those with KRAS wild-type tumors.
  • No difference in overall survival was observed.

In a phase III ARCHER 1009 trial reported in The Lancet Oncology, Ramalingam et al found no progression-free survival benefit of the irreversible pan-HER tyrosine kinase inhibitor dacomitinib vs erlotinib among all patients with pretreated non–small cell lung cancer (NSCLC) or among those with KRAS wild-type tumors.

Study Details

In this double-blind trial, 878 patients from 134 centers in 23 countries with locally advanced or metastatic NSCLC and progression after one or two previous chemotherapy regimens were randomly assigned between June 2011 and March 2013 to receive oral dacomitinib at 45 mg/d (n = 439 [256 of which were KRAS wild-type tumors]) or erlotinib at 150 mg/d (n = 439 [263 of which were KRAS wild-type tumors]). Randomization was stratified by histology, ethnicity, Eastern Cooperative Oncology Group performance status, and smoking status. The coprimary endpoints were progression-free survival on independent review for all patients and for the subgroup with KRAS wild-type tumors.

The dacomitinib and erlotinib groups were generally balanced for age (median, 64 and 62 years, 48% and 39% ≥ 65 years), sex (66% and 63% male), ethnicity (76% and 75% white, 21% and 20% Asian), histology (adenocarcinoma in 69% and 68%), disease stage (IV in 91% and 92%), never-smoker status (18% and 19%), KRAS status (wild-type in 58% and 60%, mutant in 16% and 15%, unknown in 26% and 25%), EGFR status (wild-type in 74% and 76%, mutant in 11% and 10%, unknown in 15% and 14%), and number of previous systemic therapies (1 in 58% and 64%, 2 in 40% and 33%).

No Progression-Free Survival Differences

Median follow-up for all patients was 7.1 months. Median progression-free survival was 2.6 months (95% confidence interval [CI] = 1.9–2.8) in both the dacomitinib group and the erlotinib group (stratified hazard ratio [HR] = 0.941, P = .229). Among patients with wild-type KRAS, median progression-free survival was 2.6 months (95% CI = 1.9–2.9) vs 2.6 months (95% CI = 1.9–3.0; stratified HR = 1.022, P = .587).

Median overall survival was 7.9 vs 8.4 months in the overall population (HR = 1.079, P = .817) and 8.1 vs 8.5 months (HR = 1.095, P = .796) in the subgroup with wild-type KRAS. No significant differences between treatments in progression-free survival or overall survival were observed in any other subgroups.

Objective response was observed in 11% vs 8% (P = .083) among all patients and in 13% vs 11% (P = .261) in the KRAS wild-type subgroup.

Adverse Events

Serious adverse events occurred in 12% of the dacomitinib group vs 9% of the erlotinib group. The most common grade 3 or 4 adverse events were diarrhea (11% vs 2%), rash (7% vs 3%), and stomatitis (3% vs < 1%).

The investigators concluded: “Irreversible EGFR inhibition with dacomitinib was not superior to erlotinib in an unselected patient population with advanced non-small-cell lung cancer or in patients with KRAS wild-type tumours. Further study of irreversible EGFR inhibitors should be restricted to patients with activating EGFR mutations.”

Suresh S. Ramalingam, MD, of Emory University School of Medicine, is the corresponding author for The Lancet Oncology article.

The study was funded by Pfizer. For full disclosures of the study authors, visit

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