title: Randomized phase II trial of erlotinib alone or with carboplatin and paclitaxel in patients who were never or light former smokers with advanced lung adenocarcinoma: CALGB 30406 trial.
abstract: OBJECTIVE
  Erlotinib is clinically effective in patients with non-small-cell lung cancer (NSCLC) who have adenocarcinoma, are never or limited former smokers, or have EGFR mutant tumors. We investigated the efficacy of erlotinib alone or in combination with chemotherapy in patients with these characteristics.
  
  
  METHODS
  Patients with advanced NSCLC (adenocarcinoma) who were epidermal growth factor receptor tyrosine kinase inhibitor and chemotherapy naive never or light former smokers (smokers of > 100 cigarettes and ≤ 10 pack years and quit ≥ 1 year ago) were randomly assigned to continuous erlotinib or in combination with carboplatin and paclitaxel (ECP) for six cycles followed by erlotinib alone. The primary end point was progression-free survival (PFS). Tissue collection was mandatory.
  
  
  RESULTS
  PFS was similar (5.0 v 6.6 months; P = .1988) in patients randomly assigned to erlotinib alone (arm A; n = 81) or to ECP (arm B; n = 100). EGFR mutation analysis was possible in 91% (164 of 181) of patients, and EGFR mutations were detected in 40% (51 of 128) of never smokers and in 42% (15 of 36) of light former smokers. In arm A, response rate (70% v 9%), PFS (14.1 v 2.6 months), and overall survival (OS; 31.3 v 18.1 month) favored EGFR-mutant patients. In arm B, response rate (73% v 30%), PFS (17.2 v 4.8 months), and OS (38.1 v 14.4 months) favored EGFR-mutant patients. Incidence of grades 3 to 4 hematologic (2% v 49%; P < .001) and nonhematologic (24% v 52%; P < .001) toxicity was greater in patients treated with ECP.
  
  
  CONCLUSIONS
  Erlotinib and erlotinib plus chemotherapy have similar efficacy in clinically selected populations of patients with advanced NSCLC. EGFR mutations identify patients most likely to benefit.
authors.affiliation: Dana-Farber Cancer Institute and Brigham and Women’s Hospital, Boston, MA, USA. pjanne@partners.org
authors.forename: Pasi A
authors.initials: PA
authors.lastname: Jänne
authors.forename: Xiaofei
authors.initials: X
authors.lastname: Wang
authors.forename: Mark A
authors.initials: MA
authors.lastname: Socinski
authors.forename: Jeffrey
authors.initials: J
authors.lastname: Crawford
authors.forename: Thomas E
authors.initials: TE
authors.lastname: Stinchcombe
authors.forename: Lin
authors.initials: L
authors.lastname: Gu
authors.forename: Marzia
authors.initials: M
authors.lastname: Capelletti
authors.forename: Martin J
authors.initials: MJ
authors.lastname: Edelman
authors.forename: Miguel A
authors.initials: MA
authors.lastname: Villalona-Calero
authors.forename: Robert
authors.initials: R
authors.lastname: Kratzke
authors.forename: Everett E
authors.initials: EE
authors.lastname: Vokes
authors.forename: Vincent A
authors.initials: VA
authors.lastname: Miller
mesh_terms: D000230:Adenocarcinoma / Q000188:drug therapy*; D000077192:Adenocarcinoma of Lung; D000328:Adult; D000368:Aged; D000369:Aged, 80 and over; D000971:Antineoplastic Combined Chemotherapy Protocols / Q000627:therapeutic use*; D016190:Carboplatin / Q000008:administration & dosage*; D018572:Disease-Free Survival; D066246:ErbB Receptors / Q000235:genetics; D000069347:Erlotinib Hydrochloride; D005260:Female; D006801:Humans; D008175:Lung Neoplasms / Q000188:drug therapy*; D008297:Male; D008875:Middle Aged; D010919:Placebos; D011799:Quinazolines / Q000008:administration & dosage*; D012907:Smoking / Q000009:adverse effects*
chemical_list: D010919:Placebos; D011799:Quinazolines; D016190:Carboplatin; D000069347:Erlotinib Hydrochloride; D066246:ErbB Receptors