title: Factor associated with failure to administer subsequent treatment after progression in the first-line chemotherapy in EGFR-mutant non-small cell lung cancer: Okayama Lung Cancer Study Group experience.
abstract: OBJECTIVE
  Early administration of both epidermal growth factor receptor-tyrosine kinase inhibitor (EGFR-TKI) monotherapy and cytotoxic chemotherapy is crucial for non-small cell lung cancer (NSCLC) patients harboring EGFR mutations. We investigated the effect of first-line administration of these therapies on subsequent therapy in NSCLC patients.
  
  
  METHODS
  This study enrolled 63 consecutive patients with advanced EGFR-mutant NSCLC and good performance status (PS) and who underwent first-line EGFR-TKI therapy or standard cytotoxic chemotherapy and then had progressive disease, from 2007 to 2011. The ability of each patient to receive the other therapy after first-line treatment failure was assessed.
  
  
  RESULTS
  In the first-line setting, 23 and 40 patients received EGFR-TKI therapy and cytotoxic chemotherapy, respectively. At relapse, the EGFR-TKI therapy group showed more frequent PS deterioration (p = 0.042) and greater likelihood of symptomatic central nervous system (CNS) relapse (p = 0.093) compared with the cytotoxic chemotherapy group. Nine (39 %) of 23 patients initially receiving EGFR-TKI therapy could not receive standard cytotoxic therapy after progression mainly due to symptomatic CNS relapse. Only one (3 %) of 40 initially treated with cytotoxic chemotherapy failed to receive subsequent EGFR-TKI therapy (p < 0.001). Multivariate analysis revealed a correlation between the first-line therapy and the failure to switch to the other therapy after disease progression (OR 48.605, p = 0.005).
  
  
  CONCLUSIONS
  In this study, patients who could not receive both EGFR-TKI therapy and cytotoxic chemotherapy in the early-line setting were included more in the first-line EGFR-TKI group, suggesting a potential risk associated with missing the timing of administration of subsequent therapy. Further investigation is warranted to detect their pretreatment clinical or molecular characteristics for development of a new treatment strategy specific for such subpopulation.
authors.affiliation: Department of Respiratory Medicine, Okayama University Hospital, 2-5-1, Shikata-cho, Kitaku, Okayama, 700-8558, Japan.
authors.forename: Yuka
authors.initials: Y
authors.lastname: Kato
authors.forename: Katsuyuki
authors.initials: K
authors.lastname: Hotta
authors.forename: Nagio
authors.initials: N
authors.lastname: Takigawa
authors.forename: Naoyuki
authors.initials: N
authors.lastname: Nogami
authors.forename: Toshiyuki
authors.initials: T
authors.lastname: Kozuki
authors.forename: Akiko
authors.initials: A
authors.lastname: Sato
authors.forename: Eiki
authors.initials: E
authors.lastname: Ichihara
authors.forename: Kenichiro
authors.initials: K
authors.lastname: Kudo
authors.forename: Isao
authors.initials: I
authors.lastname: Oze
authors.forename: Masahiro
authors.initials: M
authors.lastname: Tabata
authors.forename: Tetsu
authors.initials: T
authors.lastname: Shinkai
authors.forename: Mitsune
authors.initials: M
authors.lastname: Tanimoto
authors.forename: Katsuyuki
authors.initials: K
authors.lastname: Kiura
mesh_terms: D000328:Adult; D000368:Aged; D000369:Aged, 80 and over; D000970:Antineoplastic Agents / Q000009:adverse effects / Q000627:therapeutic use*; D002289:Carcinoma, Non-Small-Cell Lung / Q000188:drug therapy*; D018450:Disease Progression; D004358:Drug Therapy / Q000379:methods*; D066246:ErbB Receptors / Q000235:genetics / Q000627:therapeutic use*; D005260:Female; D006801:Humans; D008175:Lung Neoplasms / Q000188:drug therapy*; D008297:Male; D008875:Middle Aged; D012189:Retrospective Studies
chemical_list: D000970:Antineoplastic Agents; D066246:ErbB Receptors