title: Efficacy and safety of trastuzumab as a single agent in first-line treatment of HER2-overexpressing metastatic breast cancer.
abstract: OBJECTIVE
  To evaluate the efficacy and safety of first-line, single-agent trastuzumab in women with HER2-overexpressing metastatic breast cancer.
  
  
  METHODS
  One hundred fourteen women with HER2-overexpressing metastatic breast cancer were randomized to receive first-line treatment with trastuzumab 4 mg/kg loading dose, followed by 2 mg/kg weekly, or a higher 8 mg/kg loading dose, followed by 4 mg/kg weekly.
  
  
  RESULTS
  The objective response rate was 26% (95% confidence interval [CI], 18.2% to 34.4%), with seven complete and 23 partial responses. Response rates in 111 assessable patients with 3+ and 2+ HER2 overexpression by immunohistochemistry (IHC) were 35% (95% CI, 24.4% to 44.7%) and none (95% CI, 0% to 15.5%), respectively. The clinical benefit rates in assessable patients with 3+ and 2+ HER2 overexpression were 48% and 7%, respectively. The response rates in 108 assessable patients with and without HER2 gene amplification by fluorescence in situ hybridization (FISH) analysis were 34% (95% CI, 23.9% to 45.7%) and 7% (95% CI, 0.8% to 22.8%), respectively. Seventeen (57%) of 30 patients with an objective response and 22 (51%) of 43 patients with clinical benefit had not experienced disease progression at follow-up at 12 months or later. The most common treatment-related adverse events were chills (25% of patients), asthenia (23%), fever (22%), pain (18%), and nausea (14%). Cardiac dysfunction occurred in two patients (2%); both had histories of cardiac disease and did not require additional intervention after discontinuation of trastuzumab. There was no clear evidence of a dose-response relationship for response, survival, or adverse events.
  
  
  CONCLUSIONS
  Single-agent trastuzumab is active and well tolerated as first-line treatment of women with metastatic breast cancer with HER2 3+ overexpression by IHC or gene amplification by FISH.
authors.affiliation: University of Miami School of Medicine, Comprehensive Cancer Research Group Inc, and Columbia Cancer Research Network of Florida, Miami, FL, USA.
authors.forename: Charles L
authors.initials: CL
authors.lastname: Vogel
authors.forename: Melody A
authors.initials: MA
authors.lastname: Cobleigh
authors.forename: Debu
authors.initials: D
authors.lastname: Tripathy
authors.forename: John C
authors.initials: JC
authors.lastname: Gutheil
authors.forename: Lyndsay N
authors.initials: LN
authors.lastname: Harris
authors.forename: Louis
authors.initials: L
authors.lastname: Fehrenbacher
authors.forename: Dennis J
authors.initials: DJ
authors.lastname: Slamon
authors.forename: Maureen
authors.initials: M
authors.lastname: Murphy
authors.forename: William F
authors.initials: WF
authors.lastname: Novotny
authors.forename: Michael
authors.initials: M
authors.lastname: Burchmore
authors.forename: Steven
authors.initials: S
authors.lastname: Shak
authors.forename: Stanford J
authors.initials: SJ
authors.lastname: Stewart
authors.forename: Michael
authors.initials: M
authors.lastname: Press
mesh_terms: D000328:Adult; D000368:Aged; D000369:Aged, 80 and over; D000911:Antibodies, Monoclonal / Q000008:administration & dosage / Q000009:adverse effects / Q000627:therapeutic use*; D061067:Antibodies, Monoclonal, Humanized; D000970:Antineoplastic Agents / Q000008:administration & dosage / Q000009:adverse effects / Q000627:therapeutic use*; D001943:Breast Neoplasms / Q000188:drug therapy* / Q000235:genetics; D005260:Female; D005784:Gene Amplification; D018734:Genes, erbB-2 / Q000235:genetics*; D006801:Humans; D007150:Immunohistochemistry; D017403:In Situ Hybridization; D008875:Middle Aged; D011788:Quality of Life; D012449:Safety; D000068878:Trastuzumab; D016896:Treatment Outcome
chemical_list: D000911:Antibodies, Monoclonal; D061067:Antibodies, Monoclonal, Humanized; D000970:Antineoplastic Agents; D000068878:Trastuzumab