title: Single-agent lapatinib for HER2-overexpressing advanced or metastatic breast cancer that progressed on first- or second-line trastuzumab-containing regimens.
abstract: BACKGROUND
  This phase II study evaluated the efficacy and safety of lapatinib in patients with human epidermal growth factor receptor 2 (HER2)-positive advanced or metastatic breast cancer that progressed during prior trastuzumab therapy.
  
  
  METHODS
  Women with stage IIIB/IV HER2-overexpressing breast cancer were treated with single-agent lapatinib 1250 or 1500 mg once daily after protocol amendment. Tumor response according to RECIST was assessed every 8 weeks. HER2 expression was assessed in tumor tissue by immunohistochemistry and FISH.
  
  
  RESULTS
  Seventy-eight patients were enrolled in the study. Investigator and independent review response rates [complete response (CR) or partial response (PR)] were 7.7% and 5.1%, and clinical benefit rates (CR, PR, or stable disease for >or=24 weeks) were 14.1% and 9.0%, respectively. Median time to progression was 15.3 weeks by independent review, and median overall survival was 79 weeks. The most common treatment-related adverse events were rash (47%), diarrhea (46%), nausea (31%), and fatigue (18%).
  
  
  CONCLUSIONS
  Single-agent lapatinib has clinical activity with manageable toxic effects in HER2-overexpressing breast cancer that progressed on trastuzumab-containing therapy. Studies of lapatinib-based combination regimens with chemotherapy and other targeted therapies in metastatic and earlier stages of breast cancer are warranted.
authors.affiliation: Department of Medicine/Medical Oncology, Duke University Medical Center, Durham, NC 27710, USA. black034@mc.duke.edu
authors.forename: K L
authors.initials: KL
authors.lastname: Blackwell
authors.forename: M D
authors.initials: MD
authors.lastname: Pegram
authors.forename: E
authors.initials: E
authors.lastname: Tan-Chiu
authors.forename: L S
authors.initials: LS
authors.lastname: Schwartzberg
authors.forename: M C
authors.initials: MC
authors.lastname: Arbushites
authors.forename: J D
authors.initials: JD
authors.lastname: Maltzman
authors.forename: J K
authors.initials: JK
authors.lastname: Forster
authors.forename: S D
authors.initials: SD
authors.lastname: Rubin
authors.forename: S H
authors.initials: SH
authors.lastname: Stein
authors.forename: H J
authors.initials: HJ
authors.lastname: Burstein
mesh_terms: D000328:Adult; D000368:Aged; D000911:Antibodies, Monoclonal / Q000627:therapeutic use; D061067:Antibodies, Monoclonal, Humanized; D000970:Antineoplastic Agents / Q000627:therapeutic use*; D001943:Breast Neoplasms / Q000188:drug therapy* / Q000378:metabolism* / Q000473:pathology / Q000556:secondary; D018450:Disease Progression; D005260:Female; D006801:Humans; D000077341:Lapatinib; D008875:Middle Aged; D011799:Quinazolines / Q000627:therapeutic use*; D018719:Erb-b2 Receptor Tyrosine Kinases / Q000096:biosynthesis; D000068878:Trastuzumab; D017211:Treatment Failure; D016896:Treatment Outcome
chemical_list: D000911:Antibodies, Monoclonal; D061067:Antibodies, Monoclonal, Humanized; D000970:Antineoplastic Agents; D000077341:Lapatinib; D011799:Quinazolines; D018719:Erb-b2 Receptor Tyrosine Kinases; D000068878:Trastuzumab