title: An open-label expanded access study of lapatinib and capecitabine in patients with HER2-overexpressing locally advanced or metastatic breast cancer.
abstract: BACKGROUND
  The Lapatinib Expanded Access Program (LEAP) was designed to provide access to lapatinib plus capecitabine for HER2-positive metastatic breast cancer patients who previously received an anthracycline, a taxane, and a trastuzumab and had no other treatment options.
  
  
  METHODS
  LEAP opened globally and enrollment continued until lapatinib received regulatory approval in each participating country. Patients were assessed for progression-free survival (PFS) and overall survival (OS) and monitored for serious adverse events (SAEs).
  
  
  RESULTS
  As of 30 September 2008, 4283 patients from 45 countries enrolled in LEAP. The median treatment duration was 24.7 weeks. The most common drug-related SAEs were diarrhea (9.7%), vomiting (4.3%), and nausea (2.4%) and were mainly grade 3 or higher. The incidences of special interest SAEs were decreased left ventricle ejection fraction (0.5%), interstitial lung disease/pneumonitis (0.2%), and serious hepatobiliary events (0.4%). This safety profile is consistent with the overall lapatinib program. The median PFS and OS were 21.1 [95% confidence interval (CI) = 20.1-22.3] and 39.6 (95% CI = 37.7-40.7) weeks, respectively (n = 4006). Subgroup analysis showed longer PFS and OS in patients who had not received prior capecitabine.
  
  
  CONCLUSIONS
  These results demonstrate the safety and efficacy of lapatinib in a broader patient population compared with a clinical trial.
authors.affiliation: Department of Medical Oncology, Fondazione IRCCS Istituto Tumori, Milano, Italy. Electronic address: giuseppe.capri@istitutotumori.mi.it.
authors.forename: G
authors.initials: G
authors.lastname: Capri
authors.affiliation: Medical Oncology Program, RS McLaughlin Durham Regional Cancer Centre, Oshawa, Ontario, Canada.
authors.forename: J
authors.initials: J
authors.lastname: Chang
authors.affiliation: Department of General Surgery, Chang Gung Memorial Hospital, Taipei, Taiwan.
authors.forename: S-C
authors.initials: SC
authors.lastname: Chen
authors.affiliation: Department of Oncology and Hematology, Universita degli Studi di Modena e Reggio Emilia, Modena, Italy.
authors.forename: P
authors.initials: P
authors.lastname: Conte
authors.affiliation: Department of Oncology, Hospital Olomouc, Olomouc, Czech Republic.
authors.forename: K
authors.initials: K
authors.lastname: Cwiertka
authors.affiliation: Department of Medical Oncology, CHU Liège Hospital du Sart-Tilman, Liège, Belgium.
authors.forename: G
authors.initials: G
authors.lastname: Jerusalem
authors.affiliation: Breast Cancer Department, The Hospital Associated With Military Medical Science, Beijing, China.
authors.forename: Z
authors.initials: Z
authors.lastname: Jiang
authors.affiliation: Department of Medical Oncology, Royal Marsden NHS Foundation Trust & Institute of Cancer Research, London, UK.
authors.forename: S
authors.initials: S
authors.lastname: Johnston
authors.affiliation: Breast Cancer Unit, Sheba Medical Center, Ramat Gan, Israel.
authors.forename: B
authors.initials: B
authors.lastname: Kaufman
authors.affiliation: Breast Link Medical Group, Inc., Long Beach, CA, USA.
authors.forename: J
authors.initials: J
authors.lastname: Link
authors.affiliation: Breast and Endocrine Cancer Branch, National Cancer Center, Kyunggi-do, South Korea.
authors.forename: J
authors.initials: J
authors.lastname: Ro
authors.affiliation: Department of Hematology and Oncology, Marien Hospital Düsseldorf, Düsseldorf, Germany.
authors.forename: J
authors.initials: J
authors.lastname: Schütte
authors.affiliation: Oncology Medicine Development Center, GlaxoSmithKline, Uxbridge, Middlesex, UK.
authors.forename: C
authors.initials: C
authors.lastname: Oliva
authors.affiliation: Oncology Medicine Development Center, GlaxoSmithKline, Uxbridge, Middlesex, UK.
authors.forename: R
authors.initials: R
authors.lastname: Parikh
authors.affiliation: Oncology Medicine Development Center, GlaxoSmithKline, Collegeville, PA, USA.
authors.forename: A
authors.initials: A
authors.lastname: Preston
authors.affiliation: Oncology Medicine Development Center, GlaxoSmithKline, Collegeville, PA, USA.
authors.forename: J
authors.initials: J
authors.lastname: Rosenlund
authors.affiliation: Oncology, Global Clinical Safety and Pharmacovigilance, GlaxoSmithKline, Collegeville, PA, USA.
authors.forename: M
authors.initials: M
authors.lastname: Selzer
authors.affiliation: Oncology Medicine Development Center, GlaxoSmithKline, Collegeville, PA, USA.
authors.forename: D
authors.initials: D
authors.lastname: Zembryki
authors.affiliation: Department of Molecular and Clinical Oncology, Universita degli Studi di Napoli Federico II, Napoli, Italy.
authors.forename: S
authors.initials: S
authors.lastname: De Placido
mesh_terms: D000328:Adult; D000368:Aged; D000369:Aged, 80 and over; D000971:Antineoplastic Combined Chemotherapy Protocols / Q000627:therapeutic use*; D001932:Brain Neoplasms / Q000188:drug therapy* / Q000378:metabolism* / Q000556:secondary; D001943:Breast Neoplasms / Q000188:drug therapy* / Q000378:metabolism* / Q000473:pathology; D000069287:Capecitabine; D003841:Deoxycytidine / Q000008:administration & dosage / Q000031:analogs & derivatives; D004334:Drug Administration Schedule; D005260:Female; D005472:Fluorouracil / Q000008:administration & dosage / Q000031:analogs & derivatives; D005500:Follow-Up Studies; D006801:Humans; D000077341:Lapatinib; D008207:Lymphatic Metastasis; D008875:Middle Aged; D011799:Quinazolines / Q000008:administration & dosage; D018719:Erb-b2 Receptor Tyrosine Kinases / Q000378:metabolism*; D012449:Safety; D015996:Survival Rate; D016896:Treatment Outcome; D055815:Young Adult
chemical_list: D000069287:Capecitabine; D003841:Deoxycytidine; D005472:Fluorouracil; D000077341:Lapatinib; D011799:Quinazolines; D018719:Erb-b2 Receptor Tyrosine Kinases