title: Safety of treatment of metastatic breast cancer with trastuzumab beyond disease progression.
abstract: OBJECTIVE
  In a pivotal phase III trial, the addition of trastuzumab to chemotherapy significantly improved response rate, time to disease progression, and overall survival in women with HER2 overexpressing metastatic breast cancer. We conducted an extension study to this trial to obtain additional safety information and to provide trastuzumab following disease progression.
  
  
  METHODS
  A total of 247 patients with documented disease progression received weekly intravenous trastuzumab in the extension study. Concurrent therapies were administered at the discretion of the treating physician. Patient groups were based on initial study treatment: chemotherapy alone (group 1, n=154) or chemotherapy plus trastuzumab (group 2, n=93).
  
  
  RESULTS
  Sixty-eight percent of group 1 and 76% of group 2 received chemotherapy plus trastuzumab in the extension trial; the remainder received trastuzumab alone or combined with palliative radiotherapy or hormonal therapy. Seventy-six percent of group 1 and 55% of group 2 experienced at least one adverse event, similar to effects observed in the pivotal trial. Symptomatic or asymptomatic cardiac dysfunction occurred in 9% of group 1 and 2% of group 2 patients. Overall objective response rates were 14% in group 1 and 11% in group 2; median durations of response exceeded 6 months in both groups.
  
  
  CONCLUSIONS
  Our results suggest that prolonged use of trastuzumab therapy is safe and well tolerated. Longer durations of therapy did not appear to increase the risk of cardiac dysfunction. Patients progressing on trastuzumab-containing therapy demonstrate some response to a second trastuzumab-containing regimen. The independent contribution of trastuzumab in this setting merits further study.
authors.affiliation: University of Texas Southwestern Medical Center at Dallas, 5323 Harry Hines Blvd, Dallas, TX 75390-8852, USA. debu.tripathy@utsouthwestern.edu
authors.forename: Debu
authors.initials: D
authors.lastname: Tripathy
authors.forename: Dennis J
authors.initials: DJ
authors.lastname: Slamon
authors.forename: Melody
authors.initials: M
authors.lastname: Cobleigh
authors.forename: Andrew
authors.initials: A
authors.lastname: Arnold
authors.forename: Mansoor
authors.initials: M
authors.lastname: Saleh
authors.forename: Joanne E
authors.initials: JE
authors.lastname: Mortimer
authors.forename: Maureen
authors.initials: M
authors.lastname: Murphy
authors.forename: Stanford J
authors.initials: SJ
authors.lastname: Stewart
mesh_terms: D000911:Antibodies, Monoclonal / Q000009:adverse effects* / Q000627:therapeutic use; D061067:Antibodies, Monoclonal, Humanized; D000970:Antineoplastic Agents / Q000009:adverse effects* / Q000627:therapeutic use; D000971:Antineoplastic Combined Chemotherapy Protocols / Q000627:therapeutic use; D001943:Breast Neoplasms / Q000188:drug therapy* / Q000473:pathology; D018450:Disease Progression; D005260:Female; D006801:Humans; D018719:Erb-b2 Receptor Tyrosine Kinases / Q000037:antagonists & inhibitors*; D012449:Safety; D000068878:Trastuzumab
chemical_list: D000911:Antibodies, Monoclonal; D061067:Antibodies, Monoclonal, Humanized; D000970:Antineoplastic Agents; D018719:Erb-b2 Receptor Tyrosine Kinases; D000068878:Trastuzumab