title: Dacomitinib versus erlotinib in patients with EGFR-mutated advanced nonsmall-cell lung cancer (NSCLC): pooled subset analyses from two randomized trials.
abstract: BACKGROUND
  The 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.
  
  
  METHODS
  The 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.
  
  
  RESULTS
  One 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.
  
  
  CONCLUSIONS
  Dacomitinib 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).
  
  
  BACKGROUND
  ARCHER 1009 (NCT01360554) and A7471028 (NCT00769067).
authors.affiliation: Department of Hematology and Medical Oncology, Winship Cancer Institute of Emory University, Atlanta, USA suresh.ramalingam@emory.edu.
authors.forename: S S
authors.initials: SS
authors.lastname: Ramalingam
authors.affiliation: Department of Oncology, Princess Alexandra Hospital, Woolloongabba, Brisbane.
authors.forename: K
authors.initials: K
authors.lastname: O'Byrne
authors.affiliation: Department of Oncology, Chris O'Brien Lifehouse, Camperdown, Sydney, Australia.
authors.forename: M
authors.initials: M
authors.lastname: Boyer
authors.affiliation: Clinical Oncology, The Chinese University of Hong Kong, Shatin, Hong Kong.
authors.forename: T
authors.initials: T
authors.lastname: Mok
authors.affiliation: Dana Farber Cancer Institute, Boston.
authors.forename: P A
authors.initials: PA
authors.lastname: Jänne
authors.affiliation: Pfizer Oncology, New York, USA.
authors.forename: H
authors.initials: H
authors.lastname: Zhang
authors.affiliation: Pfizer Oncology, New York, USA.
authors.forename: J
authors.initials: J
authors.lastname: Liang
authors.affiliation: Pfizer Oncology, New York, USA.
authors.forename: I
authors.initials: I
authors.lastname: Taylor
authors.affiliation: Pfizer Oncology, New York, USA.
authors.forename: E I
authors.initials: EI
authors.lastname: Sbar
authors.affiliation: Department of Oncology, Doce de Octubre University Hospital & CNIO, Madrid, Spain.
authors.forename: L
authors.initials: L
authors.lastname: Paz-Ares
mesh_terms: D000328:Adult; D000368:Aged; D000369:Aged, 80 and over; D000970:Antineoplastic Agents / Q000627:therapeutic use*; D002289:Carcinoma, Non-Small-Cell Lung / Q000188:drug therapy*; D018572:Disease-Free Survival; D066246:ErbB Receptors / Q000037:antagonists & inhibitors* / Q000235:genetics; D000069347:Erlotinib Hydrochloride / Q000009:adverse effects / Q000627:therapeutic use*; D005260:Female; D006801:Humans; D008175:Lung Neoplasms / Q000188:drug therapy*; D008297:Male; D008875:Middle Aged; D009154:Mutation; D047428:Protein Kinase Inhibitors / Q000627:therapeutic use*; D052999:Quinazolinones / Q000009:adverse effects / Q000627:therapeutic use*
chemical_list: D000970:Antineoplastic Agents; D047428:Protein Kinase Inhibitors; D052999:Quinazolinones; C525726:dacomitinib; D000069347:Erlotinib Hydrochloride; C512478:EGFR protein, human; D066246:ErbB Receptors
keywords: EGFR mutation; NSCLC; dacomitinib; erlotinib; tyrosine kinase inhibitor