title: A prospective, multicenter phase II trial of low-dose erlotinib as maintenance treatment after platinum doublet chemotherapy for advanced non-small cell lung cancer harboring EGFR mutation.
abstract: BACKGROUND
  Maintenance therapy with full-dose erlotinib for patients with advanced non-small cell lung cancer (NSCLC) has demonstrated a significant overall survival (OS) benefit. However, 150 mg/day of erlotinib seems too toxic as maintenance therapy. This study aimed to evaluate the efficacy and safety of low-dose erlotinib (25 mg/day) as maintenance treatment after platinum doublet chemotherapy in NSCLC harboring epidermal growth factor receptor (EGFR) mutation.
  
  
  METHODS
  Activated EGFR-mutation-positive NSCLC patients who did not progress after first-line platinum-doublet chemotherapy, ≥20 and ≤85 years old, with performance status (PS) 0-3 were included in this study. Low-dose erlotinib (25 mg/day) was administered until disease progression. The primary endpoint was overall response rate (ORR). Secondary endpoints included progression-free survival (PFS), OS, and safety. The required sample size was 40 patients.
  
  
  RESULTS
  The study was stopped early, after achieving only 28% of planned enrollment, due to poor accrual. Between April 2011 and May 2014, 11 patients (male/female, 5/6; median age, 72 years; PS 0/1, 8/3; stage IV/relapse after surgery, 9/2; exon 19 deletions/L858R, 7/4) were enrolled and accessible in this study. Partial response (PR) was observed in 6 patients (56%). Median PFS was 14.9 months [95% confidence interval (CI), 2.7-27.1 months] and median OS was not calculable. Toxicities were generally mild. Only one patient developed grade 3 aspartate aminotransferase (AST)/alanine aminotransferase (ALT) elevation. Eight patients developed grade 1 skin rash. No treatment-related deaths were observed. Eight patients progressed, and recurrences included brain metastases (n=3), local recurrence (n=2), local recurrence plus brain metastasis (n=1), bone metastasis (n=1), and pulmonary metastasis (n=1).
  
  
  CONCLUSIONS
  The study was stopped early due to poor accrual. However, our study suggests that maintenance therapy with low-dose erlotinib might be useful and tolerable in selected NSCLC patients harboring EGFR mutation.
authors.affiliation: Department of Medical Oncology, Funabashi Municipal Medical Center, 1-21-1 Kanasugi, Chiba 273-8588, Japan; Department of Respiratory Medicine, National Center for Global Health and Medicine, 1-11-1 Toyama, Tokyo 162-0056, Japan. shirano@mmc.funabashi.chiba.jp.
authors.forename: Satoshi
authors.initials: S
authors.lastname: Hirano
authors.affiliation: Department of Respiratory Medicine, National Center for Global Health and Medicine, 1-11-1 Toyama, Tokyo 162-0056, Japan.
authors.forename: Go
authors.initials: G
authors.lastname: Naka
authors.affiliation: Department of Respiratory Medicine, National Center for Global Health and Medicine, 1-11-1 Toyama, Tokyo 162-0056, Japan.
authors.forename: Yuichiro
authors.initials: Y
authors.lastname: Takeda
authors.affiliation: Department of Respiratory Medicine, National Center for Global Health and Medicine, 1-11-1 Toyama, Tokyo 162-0056, Japan.
authors.forename: Motoyasu
authors.initials: M
authors.lastname: Iikura
authors.affiliation: Department of Respiratory Medicine, Funabashi Municipal Medical Center, 1-21-1 Kanasugi, Chiba 273-8588, Japan.
authors.forename: Noriko
authors.initials: N
authors.lastname: Hayama
authors.affiliation: Department of Respiratory Medicine, Funabashi Municipal Medical Center, 1-21-1 Kanasugi, Chiba 273-8588, Japan.
authors.forename: Asako
authors.initials: A
authors.lastname: Yanagisawa
authors.affiliation: Department of Respiratory Medicine, Funabashi Municipal Medical Center, 1-21-1 Kanasugi, Chiba 273-8588, Japan.
authors.forename: Hiroyuki
authors.initials: H
authors.lastname: Amano
authors.affiliation: Department of Respiratory Medicine, Funabashi Municipal Medical Center, 1-21-1 Kanasugi, Chiba 273-8588, Japan.
authors.forename: Makoto
authors.initials: M
authors.lastname: Nakamura
authors.affiliation: Department of Respiratory Medicine, Funabashi Municipal Medical Center, 1-21-1 Kanasugi, Chiba 273-8588, Japan.
authors.forename: Sukeyuki
authors.initials: S
authors.lastname: Nakamura
authors.affiliation: Department of Respiratory Medicine, Funabashi Municipal Medical Center, 1-21-1 Kanasugi, Chiba 273-8588, Japan.
authors.forename: Hiroshi
authors.initials: H
authors.lastname: Tabeta
authors.affiliation: Department of Respiratory Medicine, National Center for Global Health and Medicine, 1-11-1 Toyama, Tokyo 162-0056, Japan.
authors.forename: Haruhito
authors.initials: H
authors.lastname: Sugiyama
mesh_terms: D000368:Aged; D000971:Antineoplastic Combined Chemotherapy Protocols / Q000627:therapeutic use; D000068258:Bevacizumab / Q000008:administration & dosage; D016190:Carboplatin / Q000008:administration & dosage; D002289:Carcinoma, Non-Small-Cell Lung / Q000188:drug therapy* / Q000201:enzymology / Q000235:genetics / Q000473:pathology; D002945:Cisplatin / Q000008:administration & dosage; D066246:ErbB Receptors / Q000235:genetics*; D000069347:Erlotinib Hydrochloride / Q000008:administration & dosage*; D005260:Female; D006801:Humans; D008175:Lung Neoplasms / Q000188:drug therapy* / Q000201:enzymology / Q000235:genetics / Q000473:pathology; D060046:Maintenance Chemotherapy; D008297:Male; D008875:Middle Aged; D009154:Mutation; D000068437:Pemetrexed / Q000008:administration & dosage; D011446:Prospective Studies; D016896:Treatment Outcome
chemical_list: D000068437:Pemetrexed; D000068258:Bevacizumab; D016190:Carboplatin; D000069347:Erlotinib Hydrochloride; C512478:EGFR protein, human; D066246:ErbB Receptors; D002945:Cisplatin
keywords: EGFR mutation; Low-dose erlotinib; maintenance treatment; non-small cell lung cancer (NSCLC)