title: A phase II trial of saracatinib, an inhibitor of src kinases, in previously-treated advanced non-small-cell lung cancer: the princess margaret hospital phase II consortium.
abstract: BACKGROUND
  The src family of kinases may play a role in the malignant phenotype through effects on migration, motility, adhesion and proliferation. The activity of saracatinib, an orally available inhibitor of src kinases, was evaluated in patients with advanced, platinum-pretreated NSCLC.
  
  
  METHODS
  Eligible patients with advanced NSCLC of any histologic subtype and who had obtained a best response to prior platinum-based chemotherapy of at least stable disease received saracatanib 175 mg orally daily in a 28 day cycle. The primary end point was the proportion of patients progression-free after 4 cycles (16 weeks) of therapy; 8 such patients of 32 evaluable were required to deem the therapy active. Immunohistochemistry for src expression was performed on archival tissue from enrolled patients.
  
  
  RESULTS
  Thirty-seven patients received a median of 2 cycles (range, 1-14) each. Six of 31 evaluable patients were progression-free at 16 weeks. Two partial responses were observed, lasting 3.7 and 14.6 months; 1 responder had an EGFR exon 19 deletion. An additional 4 patients had stable disease for at least 4 cycles. The median progression-free and overall survival times were 1.8 and 7.6 months. No correlation between src protein expression and outcome was observed.
  
  
  CONCLUSIONS
  There may be a subset of saracatinib-responsive NSCLC that is currently molecularly undefined. Further studies of this agent in a population preselected for target mutations that potentially relevant to src pathways, such as EGFR, should be considered.
authors.affiliation: The Ottawa Hospital Cancer Centre, University of Ottawa, Ottawa, Ontario. Electronic address: slaurie@toh.on.ca.
authors.forename: Scott A
authors.initials: SA
authors.lastname: Laurie
authors.affiliation: The Ottawa Hospital Cancer Centre, University of Ottawa, Ottawa, Ontario.
authors.forename: Glenwood D
authors.initials: GD
authors.lastname: Goss
authors.affiliation: Princess Margaret Hospital, University of Toronto, Toronto, Ontario.
authors.forename: Frances A
authors.initials: FA
authors.lastname: Shepherd
authors.affiliation: The Ottawa Hospital Cancer Centre, University of Ottawa, Ottawa, Ontario.
authors.forename: M Neil
authors.initials: MN
authors.lastname: Reaume
authors.affiliation: The Ottawa Hospital Cancer Centre, University of Ottawa, Ottawa, Ontario.
authors.forename: Garth
authors.initials: G
authors.lastname: Nicholas
authors.affiliation: Princess Margaret Hospital, University of Toronto, Toronto, Ontario.
authors.forename: Lindsay
authors.initials: L
authors.lastname: Philip
authors.affiliation: Princess Margaret Hospital, University of Toronto, Toronto, Ontario.
authors.forename: Lisa
authors.initials: L
authors.lastname: Wang
authors.affiliation: Princess Margaret Hospital, University of Toronto, Toronto, Ontario.
authors.forename: Joerg
authors.initials: J
authors.lastname: Schwock
authors.affiliation: Montréal General Hospital, McGill University, Montréal, Québec, Canada.
authors.forename: Vera
authors.initials: V
authors.lastname: Hirsh
authors.affiliation: Princess Margaret Hospital, University of Toronto, Toronto, Ontario.
authors.forename: Amit
authors.initials: A
authors.lastname: Oza
authors.affiliation: Princess Margaret Hospital, University of Toronto, Toronto, Ontario.
authors.forename: Ming-Sound
authors.initials: MS
authors.lastname: Tsao
authors.affiliation: The Cancer Therapy Evaluation Program, Bethesda, MD.
authors.forename: John J
authors.initials: JJ
authors.lastname: Wright
authors.affiliation: Princess Margaret Hospital, University of Toronto, Toronto, Ontario.
authors.forename: Natasha B
authors.initials: NB
authors.lastname: Leighl
mesh_terms: D000230:Adenocarcinoma / Q000188:drug therapy* / Q000401:mortality / Q000473:pathology; D000328:Adult; D000368:Aged; D052117:Benzodioxoles / Q000627:therapeutic use*; D002289:Carcinoma, Non-Small-Cell Lung / Q000188:drug therapy* / Q000401:mortality / Q000473:pathology; D002294:Carcinoma, Squamous Cell / Q000188:drug therapy* / Q000401:mortality / Q000473:pathology; D018450:Disease Progression; D005260:Female; D005500:Follow-Up Studies; D006801:Humans; D008175:Lung Neoplasms / Q000188:drug therapy* / Q000401:mortality / Q000473:pathology; D008297:Male; D008875:Middle Aged; D060787:Neoplasm Grading; D009364:Neoplasm Recurrence, Local / Q000188:drug therapy* / Q000401:mortality / Q000473:pathology; D011379:Prognosis; D047428:Protein Kinase Inhibitors / Q000627:therapeutic use*; D011799:Quinazolines / Q000627:therapeutic use*; D015996:Survival Rate; D019061:src-Family Kinases / Q000037:antagonists & inhibitors*
chemical_list: D052117:Benzodioxoles; D047428:Protein Kinase Inhibitors; D011799:Quinazolines; C515233:saracatinib; D019061:src-Family Kinases
keywords: Biomarker; Non–small cell; Src inhibitor; Systemic therapy