title: Survival Outcomes in EGFR Mutation-Positive Lung Cancer Patients Treated with Gefitinib until or beyond Progression.
abstract: BACKGROUND
  Discontinuation of gefitinib treatment is often accompanied by a disease flare. Some studies have demonstrated a benefit of the use of epidermal growth factor receptor (EGFR) tyrosine kinase inhibitors (TKI) beyond progression; however, long-term results of these investigations remain limited.
  
  
  METHODS
  We observed 70 patients with EGFR-mutated (EGFR-M+) non-small cell lung cancer (NSCLC) receiving single-agent gefitinib in a routine clinical setting; 56 patients were experiencing RECIST progression at the time of the analysis.
  
  
  RESULTS
  There was a significant increase (p = 0.00001) in overall survival (OS) in patients continuing on gefitinib beyond progression (n = 21; median duration of continued gefitinib use: 4.2 months; median OS: not reached; expected OS: 29.7 months) as compared to those who stopped gefitinib treatment upon disease progression (n = 35; median OS: 14.0 months). The association between extended gefitinib use and improved OS remained true in multivariate Cox regression analysis (hazard ratio = 4.49, 95% confidence interval 1.25-16.09; p = 0.021). Patient selection bias constitutes an essential limitation of this clinical observational study, given that patients with a more favorable disease course and/or high initial tumor sensitivity to TKI treatment were more likely to be considered for prolonged gefitinib use.
  
  
  CONCLUSIONS
  This study confirms that continued administration of gefitinib beyond progression is a viable treatment option for some patients with EGFR-M+ NSCLC, in particular those who cannot be rescued by novel EGFR mutation-specific inhibitors such as osimertinib.
authors.affiliation: City Cancer Center, St.-Petersburg, Russia.
authors.forename: Fedor V
authors.initials: FV
authors.lastname: Moiseyenko
authors.forename: Vladimir M
authors.initials: VM
authors.lastname: Moiseyenko
authors.forename: Svetlana N
authors.initials: SN
authors.lastname: Aleksakhina
authors.forename: Vyacheslav A
authors.initials: VA
authors.lastname: Chubenko
authors.forename: Nikita M
authors.initials: NM
authors.lastname: Volkov
authors.forename: Kseniya S
authors.initials: KS
authors.lastname: Kozyreva
authors.forename: Michail M
authors.initials: MM
authors.lastname: Kramchaninov
authors.forename: Alexandr S
authors.initials: AS
authors.lastname: Zhuravlev
authors.forename: Kseniya V
authors.initials: KV
authors.lastname: Shelekhova
authors.forename: Alexandr O
authors.initials: AO
authors.lastname: Ivantsov
authors.forename: Aigul R
authors.initials: AR
authors.lastname: Venina
authors.forename: Elena V
authors.initials: EV
authors.lastname: Preobrazhenskaya
authors.forename: Natalia V
authors.initials: NV
authors.lastname: Mitiushkina
authors.forename: Aglaya G
authors.initials: AG
authors.lastname: Iyevleva
authors.forename: Evgeny N
authors.initials: EN
authors.lastname: Imyanitov
mesh_terms: D000328:Adult; D000368:Aged; D000369:Aged, 80 and over; D000970:Antineoplastic Agents / Q000008:administration & dosage; D002289:Carcinoma, Non-Small-Cell Lung / Q000188:drug therapy* / Q000235:genetics / Q000401:mortality*; D018450:Disease Progression; D018572:Disease-Free Survival; D066246:ErbB Receptors / Q000235:genetics*; D005260:Female; D000077156:Gefitinib; D020022:Genetic Predisposition to Disease / Q000453:epidemiology / Q000235:genetics; D006801:Humans; D008175:Lung Neoplasms / Q000188:drug therapy* / Q000401:mortality*; D008297:Male; D008875:Middle Aged; D009154:Mutation / Q000235:genetics; D009364:Neoplasm Recurrence, Local / Q000235:genetics / Q000401:mortality / Q000517:prevention & control; D015995:Prevalence; D011799:Quinazolines / Q000008:administration & dosage*; D012307:Risk Factors; D012426:Russia / Q000453:epidemiology; D016896:Treatment Outcome
chemical_list: D000970:Antineoplastic Agents; D011799:Quinazolines; C512478:EGFR protein, human; D066246:ErbB Receptors; D000077156:Gefitinib