title: Treatment of HER2-positive metastatic breast cancer with lapatinib and capecitabine in the lapatinib expanded access programme, including efficacy in brain metastases--the UK experience.
abstract: BACKGROUND
  The global lapatinib expanded access programme provided access to lapatinib combined with capecitabine for women with HER2-positive metastatic breast cancer (MBC) who previously received anthracycline, taxane and trastuzumab.
  
  
  METHODS
  Progression-free survival (PFS) and safety data for 356 patients recruited from the United Kingdom are reported. Efficacy was assessed in 162 patients from the five lead centres, including objective tumour response rate (ORR), time to disease progression (TTP) and efficacy in those with central nervous system (CNS) metastases. Correlation of PFS and ORR with previous capecitabine treatment was also documented.
  
  
  RESULTS
  Overall, PFS for the 356 UK patients was 21 weeks (95% CI: 17.6-24.7). In the 162 assessable patients, ORR was 21% (95% CI: 15-27%) and median TTP was 22 weeks (95% CI: 17-27). Efficacy was greater in capecitabine-naive patients (ORR 23 vs 16.3%, P=0.008). For 34 patients with CNS metastases, ORR was 21% (95% CI: 9-39%), with evidence of improvement in neurological symptoms, and median TTP was 22 weeks (95% CI: 15-28).
  
  
  CONCLUSIONS
  Lapatinib combined with capecitabine is an active treatment option for women with refractory HER2-positive MBC, including those with progressive CNS disease.
authors.affiliation: Department of Medicine, The Royal Marsden NHS Foundation Trust, Royal Marsden Hospital, Fulham Road, Chelsea and Sutton, London, UK.
authors.forename: S
authors.initials: S
authors.lastname: Sutherland
authors.forename: S
authors.initials: S
authors.lastname: Ashley
authors.forename: D
authors.initials: D
authors.lastname: Miles
authors.forename: S
authors.initials: S
authors.lastname: Chan
authors.forename: A
authors.initials: A
authors.lastname: Wardley
authors.forename: N
authors.initials: N
authors.lastname: Davidson
authors.forename: R
authors.initials: R
authors.lastname: Bhatti
authors.forename: M
authors.initials: M
authors.lastname: Shehata
authors.forename: H
authors.initials: H
authors.lastname: Nouras
authors.forename: T
authors.initials: T
authors.lastname: Camburn
authors.forename: S R D
authors.initials: SR
authors.lastname: Johnston
mesh_terms: D000328:Adult; D000368:Aged; D000971:Antineoplastic Combined Chemotherapy Protocols / Q000627:therapeutic use*; D001932:Brain Neoplasms / Q000188:drug therapy* / Q000401:mortality / Q000556:secondary; D001943:Breast Neoplasms / Q000188:drug therapy* / Q000235:genetics / Q000401:mortality / Q000473:pathology; D000069287:Capecitabine; D002277:Carcinoma / Q000188:drug therapy* / Q000235:genetics / Q000401:mortality / Q000473:pathology; D015331:Cohort Studies; D003841:Deoxycytidine / Q000008:administration & dosage / Q000031:analogs & derivatives*; D005260:Female; D005472:Fluorouracil / Q000008:administration & dosage / Q000031:analogs & derivatives*; D018734:Genes, erbB-2; D006297:Health Services Accessibility; D006801:Humans; D000077341:Lapatinib; D008875:Middle Aged; D011799:Quinazolines / Q000008:administration & dosage*; D012189:Retrospective Studies; D016019:Survival Analysis; D016896:Treatment Outcome; D006113:United Kingdom
chemical_list: D011799:Quinazolines; D000077341:Lapatinib; D003841:Deoxycytidine; D000069287:Capecitabine; D005472:Fluorouracil