title: Multinational study of the efficacy and safety of humanized anti-HER2 monoclonal antibody in women who have HER2-overexpressing metastatic breast cancer that has progressed after chemotherapy for metastatic disease.
abstract: OBJECTIVE
  Overexpression of the HER2 protein occurs in 25% to 30% of human breast cancers and leads to a particularly aggressive form of the disease. Efficacy and safety of recombinant humanized anti-HER2 monoclonal antibody as a single agent was evaluated in women with HER2-overexpressing metastatic breast cancer that had progressed after chemotherapy for metastatic disease.
  
  
  METHODS
  Two hundred twenty-two women, with HER2-overexpressing metastatic breast cancer that had progressed after one or two chemotherapy regimens, were enrolled. Patients received a loading dose of 4 mg/kg intravenously, followed by a 2-mg/kg maintenance dose at weekly intervals.
  
  
  RESULTS
  Study patients had advanced metastatic disease and had received extensive prior therapy. A blinded, independent response evaluation committee identified eight complete and 26 partial responses, for an objective response rate of 15% in the intent-to-treat population (95% confidence interval, 11% to 21%). The median duration of response was 9.1 months; the median duration of survival was 13 months. The most common adverse events, which occurred in approximately 40% of patients, were infusion-associated fever and/or chills that usually occurred only during the first infusion, and were of mild to moderate severity. These symptoms were treated successfully with acetaminophen and/or diphenhydramine. The most clinically significant adverse event was cardiac dysfunction, which occurred in 4.7% of patients. Only 1% of patients discontinued the study because of treatment-related adverse events.
  
  
  CONCLUSIONS
  Recombinant humanized anti-HER2 monoclonal antibody, administered as a single agent, produces durable objective responses and is well tolerated by women with HER2-overexpressing metastatic breast cancer that has progressed after chemotherapy for metastatic disease. Side effects that are commonly observed with chemotherapy, such as alopecia, mucositis, and neutropenia, are rarely seen.
authors.affiliation: Rush-Presbyterian-St Luke's Medical Center, Chicago, IL 60612, USA.
authors.forename: M A
authors.initials: MA
authors.lastname: Cobleigh
authors.forename: C L
authors.initials: CL
authors.lastname: Vogel
authors.forename: D
authors.initials: D
authors.lastname: Tripathy
authors.forename: N J
authors.initials: NJ
authors.lastname: Robert
authors.forename: S
authors.initials: S
authors.lastname: Scholl
authors.forename: L
authors.initials: L
authors.lastname: Fehrenbacher
authors.forename: J M
authors.initials: JM
authors.lastname: Wolter
authors.forename: V
authors.initials: V
authors.lastname: Paton
authors.forename: S
authors.initials: S
authors.lastname: Shak
authors.forename: G
authors.initials: G
authors.lastname: Lieberman
authors.forename: D J
authors.initials: DJ
authors.lastname: Slamon
mesh_terms: D000328:Adult; D000368:Aged; D000369:Aged, 80 and over; D000911:Antibodies, Monoclonal / Q000009:adverse effects / Q000493:pharmacokinetics / Q000627:therapeutic use*; D001943:Breast Neoplasms / Q000188:drug therapy / Q000378:metabolism / Q000628:therapy*; D016001:Confidence Intervals; D018450:Disease Progression; D018572:Disease-Free Survival; D005260:Female; D006331:Heart Diseases / Q000209:etiology; D006801:Humans; D008875:Middle Aged; D015999:Multivariate Analysis; D011788:Quality of Life; D018719:Erb-b2 Receptor Tyrosine Kinases / Q000276:immunology* / Q000378:metabolism; D013997:Time Factors
chemical_list: D000911:Antibodies, Monoclonal; D018719:Erb-b2 Receptor Tyrosine Kinases