title: EGFR-tyrosine kinase inhibitor treatment beyond progression in long-term Caucasian responders to erlotinib in advanced non-small cell lung cancer: a case-control study of overall survival.
abstract: BACKGROUND
  Some patients with advanced NSCLC show prolonged disease stabilization on treatment with an EGFR-tyrosine kinase inhibitor (TKI) such as erlotinib. It is not clear how to treat patients who progress after prolonged response to erlotinib. We hypothesized that TKI therapy beyond progression with added chemotherapy, radiotherapy or best supportive care may improve survival.
  
  
  METHODS
  We retrospectively analyzed all NSCLC patients treated with erlotinib at our institutions since 2004who progressed after at least stable disease on erlotinib for at least 6 months. The first 16 patients did not receive further TKI treatment after progression (controls). The following 25 patients were treated with TKI beyond progression (TKI patients). Overall survival (OS) was analyzed for the whole population, a case-control analysis of pairs matched for gender, smoking status, and histology (n=28), and for patients with known EGFR mutation status (n=23).
  
  
  RESULTS
  Treatment with TKI and chemotherapy was well tolerated. TKI-patients had a significantly longer OS from progression on TKI (case-control: median 14.5 vs. 2.0 months, HR 0.154) and longer OS from diagnosis of lung cancer (case-control: median 54.5 vs. 28.3 months, HR 0.474). An activating EGFR mutation was detected in 13 of the 23 patient tested (57%). Both among patients with and without detection of an activating EGFR mutation, those treated with erlotinib beyond progression had a longer survival.
  
  
  CONCLUSIONS
  In our case-control analysis in long-term erlotinib responders, treatment with TKI beyond progression in addition to chemotherapy or radiotherapy was feasible and lead to prolonged overall survival.
authors.affiliation: Klinik für Kardiologie und Pneumologie, Klinikum Esslingen, Hirschlandstr. 97, 73730 Esslingen, Germany. m.faehling@klinikum-es.de
authors.forename: M
authors.initials: M
authors.lastname: Faehling
authors.forename: R
authors.initials: R
authors.lastname: Eckert
authors.forename: T
authors.initials: T
authors.lastname: Kamp
authors.forename: S
authors.initials: S
authors.lastname: Kuom
authors.forename: U
authors.initials: U
authors.lastname: Griese
authors.forename: J
authors.initials: J
authors.lastname: Sträter
authors.forename: G
authors.initials: G
authors.lastname: Ott
authors.forename: W
authors.initials: W
authors.lastname: Spengler
mesh_terms: D000328:Adult; D000368:Aged; D000369:Aged, 80 and over; D002289:Carcinoma, Non-Small-Cell Lung / Q000188:drug therapy* / Q000473:pathology / Q000532:radiotherapy; D016022:Case-Control Studies; D003131:Combined Modality Therapy; D019008:Drug Resistance, Neoplasm / Q000235:genetics; D066246:ErbB Receptors / Q000235:genetics; D000069347:Erlotinib Hydrochloride; D005260:Female; D006801:Humans; D053208:Kaplan-Meier Estimate; D008175:Lung Neoplasms / Q000188:drug therapy* / Q000473:pathology / Q000532:radiotherapy; D008297:Male; D008875:Middle Aged; D009367:Neoplasm Staging; D047428:Protein Kinase Inhibitors / Q000008:administration & dosage* / Q000009:adverse effects; D011799:Quinazolines / Q000008:administration & dosage* / Q000009:adverse effects
chemical_list: D047428:Protein Kinase Inhibitors; D011799:Quinazolines; D000069347:Erlotinib Hydrochloride; C512478:EGFR protein, human; D066246:ErbB Receptors