Dacomitinib versus erlotinib in patients with EGFR-mutated advanced nonsmall-cell lung cancer (NSCLC): pooled subset analyses from two randomized trials

TLDR

"Clinical trial identifiers: ARCHER 1009 (NCT01360554), A7471028 (NCT00769067), and forthcoming ARCHER 1050 (NCT01774721)." That is concise. Let's craft each: 1. Background: "Irreversible EGFR inhibitors have shown efficacy in NSCLC with activating EGFR mutations, but it is unclear whether they outperform reversible inhibitors." 2. Purpose: "The study compared dacomitinib to erlotinib in EGFR‑mutated NSCLC patients and will evaluate dacomitinib versus gefitinib in a phase III first‑line trial." 3. Mechanism: "Patients with advanced NSCLC and confirmed exon 19 or L858R EGFR mutations were randomized in the ARCHER 1009 and A7471028 trials to receive oral dacomitinib or erlotinib, with central EGFR testing." 4.

Abstract

BackgroundThe irreversible epidermal growth factor receptor (EGFR) inhibitors have demonstrated efficacy in NSCLC patients with activating EGFR mutations, but it is unknown if they are superior to the reversible inhibitors. Dacomitinib is an oral, small-molecule irreversible inhibitor of all enzymatically active HER family tyrosine kinases.MethodsThe ARCHER 1009 (NCT01360554) and A7471028 (NCT00769067) studies randomized patients with locally advanced/metastatic NSCLC following progression with one or two prior chemotherapy regimens to dacomitinib or erlotinib. EGFR mutation testing was performed centrally on archived tumor samples. We pooled patients with exon 19 deletion and L858R EGFR mutations from both studies to compare the efficacy of dacomitinib to erlotinib.ResultsOne hundred twenty-one patients with any EGFR mutation were enrolled; 101 had activating mutations in exon 19 or 21. For patients with exon19/21 mutations, the median progression-free survival was 14.6 months [95% confidence interval (CI) 9.0–18.2] with dacomitinib and 9.6 months (95% CI 7.4–12.7) with erlotinib [unstratified hazard ratio (HR) 0.717 (95% CI 0.458–1.124), two-sided log-rank, P = 0.146]. The median survival was 26.6 months (95% CI 21.6–41.5) with dacomitinib versus 23.2 months (95% CI 16.0–31.8) with erlotinib [unstratified HR 0.737 (95% CI 0.431–1.259), two-sided log-rank, P = 0.265]. Dacomitinib was associated with a higher incidence of diarrhea and mucositis in both studies compared with erlotinib.ConclusionsDacomitinib is an active agent with comparable efficacy to erlotinib in the EGFR mutated patients. The subgroup with exon 19 deletion had favorable outcomes with dacomitinib. An ongoing phase III study will compare dacomitinib to gefitinib in first-line therapy of patients with NSCLC harboring common activating EGFR mutations (ARCHER 1050; NCT01774721).Clinical trials numberARCHER 1009 (NCT01360554) and A7471028 (NCT00769067).