title: The efficacy of lapatinib in metastatic breast cancer with HER2 non-amplified primary tumors and EGFR positive circulating tumor cells: a proof-of-concept study.
abstract: BACKGROUND
  Analysis of circulating tumor cells (CTCs) provides real-time measures of cancer sub-populations with potential for CTC-directed therapeutics. We examined whether lapatinib which binds both HER2 and EGFR could induce depletion of the EGFR-positive pool of CTCs, which may in turn lead to clinical benefits.
  
  
  METHODS
  Patients with metastatic breast cancer and HER2 non-amplified primary tumors with EGFR-positive CTCs were recruited and lapatinib 1500 mg daily was administered, in a standard two step phase 2 trial.
  
  
  RESULTS
  There were no responses leading to termination at the first analysis with 16 patients recruited out of 43 screened. In 6 out of 14 (43%) individuals eligible for the efficacy analysis, a decrease in CTCs was observed with most of these having a greater decrease in their EGFR-positive CTC pool.
  
  
  CONCLUSIONS
  This is one of the first studies of CTC-directed therapeutics and suggests that lapatinib monotherapy is not having any demonstrable clinical effects by reducing the EGFR-positive pool of CTCs in HER2 non-amplified primary tumors. Our attempt to expand the pool of patients eligible for a targeted therapy was unsuccessful; the role of clonal populations in cancer biology and therapeutic strategies to control them will require extensive evaluation in years to come.
  
  
  BACKGROUND
  Clinical trials.gov NCT00820924.
authors.affiliation: Department of Oncology, Imperial College Healthcare National Health Service Trust, Charing Cross Hospital, London, United Kingdom. j.stebbing@imperial.ac.uk
authors.forename: Justin
authors.initials: J
authors.lastname: Stebbing
authors.forename: Rachel
authors.initials: R
authors.lastname: Payne
authors.forename: Justine
authors.initials: J
authors.lastname: Reise
authors.forename: Adam E
authors.initials: AE
authors.lastname: Frampton
authors.forename: Miranda
authors.initials: M
authors.lastname: Avery
authors.forename: Laura
authors.initials: L
authors.lastname: Woodley
authors.forename: Angelo
authors.initials: A
authors.lastname: Di Leo
authors.forename: Marta
authors.initials: M
authors.lastname: Pestrin
authors.forename: Jonathan
authors.initials: J
authors.lastname: Krell
authors.forename: R Charles
authors.initials: RC
authors.lastname: Coombes
mesh_terms: D000328:Adult; D000368:Aged; D001943:Breast Neoplasms / Q000188:drug therapy* / Q000235:genetics / Q000378:metabolism / Q000473:pathology*; D066246:ErbB Receptors / Q000378:metabolism*; D005784:Gene Amplification; D006801:Humans; D000077341:Lapatinib; D008875:Middle Aged; D009360:Neoplastic Cells, Circulating / Q000187:drug effects* / Q000473:pathology; D011799:Quinazolines / Q000494:pharmacology* / Q000627:therapeutic use; D018719:Erb-b2 Receptor Tyrosine Kinases / Q000235:genetics*
chemical_list: D066246:ErbB Receptors; D000077341:Lapatinib; D011799:Quinazolines; D018719:Erb-b2 Receptor Tyrosine Kinases; C512478:EGFR protein, human; C508053:ERBB2 protein, human