title: An open-label, randomized phase II study of adecatumumab, a fully human anti-EpCAM antibody, as monotherapy in patients with metastatic breast cancer.
abstract: BACKGROUND
  High-level expression of epithelial cell adhesion molecule (EpCAM) is associated with unfavorable prognosis in breast cancer. This study was designed to investigate two doses of the fully human IgG1 anti-EpCAM antibody adecatumumab (MT201) in patients with metastatic breast cancer (MBC).
  
  
  METHODS
  A total of 109 patients were stratified into high- and low-level EpCAM expression by immunohistochemical staining of primary tumors and subsequently randomly assigned to receive monotherapy with either high- (6 mg/kg every two weeks (q2w)) or low-dose adecatumumab (2 mg/kg/ q2w) until disease progression.
  
  
  RESULTS
  No complete or partial tumor responses could be confirmed by central RECIST assessment. The probability for tumor progression was significantly lower in patients receiving high-dose adecatumumab and expressing high levels of EpCAM (hazard ratio 0.43; P = 0.0057 versus low dose and low EpCAM). Three of 18 patients with highest EpCAM expression treated with adecatumumab developed new metastases up to week 6, compared with 14 of 29 patients with low EpCAM. Most frequent treatment-related adverse events (high dose/low dose) were chills (59%/20%), nausea (55%/18%), fatigue (39%/23%) and diarrhea (43%/7%).
  
  
  CONCLUSIONS
  Single-agent adecatumumab shows dose- and target-dependent clinical activity in EpCAM-positive MBC, albeit no objective tumor regression. Further investigation of adecatumumab in patients with EpCAM-overexpressing tumors and lower tumor burden is warranted.
authors.affiliation: Department of Obstetrics and Gynecology, Johannes Gutenberg University, Mainz.
authors.forename: M
authors.initials: M
authors.lastname: Schmidt
authors.affiliation: Department of Medicine (Cancer Research), West German Cancer Center, University Hospital Essen, Essen, Germany.
authors.forename: M E
authors.initials: ME
authors.lastname: Scheulen
authors.affiliation: Third Medical Department, Centre for Oncology and Hematology, CEADDP, Applied Cancer Research, Institution for Translational Research Vienna, Vienna; Ludwig Boltzmann-Institute for Applied Cancer Research, Vienna.
authors.forename: C
authors.initials: C
authors.lastname: Dittrich
authors.affiliation: Department of Pathology, St Vinzenz Hospital, Zams, Austria.
authors.forename: P
authors.initials: P
authors.lastname: Obrist
authors.affiliation: Practice for Oncology and Hematology, Freiburg, Germany.
authors.forename: N
authors.initials: N
authors.lastname: Marschner
authors.affiliation: Medical Oncology Unit, Oncologisch Centrum Sint-Augustinus, Antwerp, Belgium.
authors.forename: L
authors.initials: L
authors.lastname: Dirix
authors.affiliation: Clinical Development, Micromet AG, Munich, Germany.
authors.forename: M
authors.initials: M
authors.lastname: Schmidt
authors.affiliation: Clinical Development, Micromet AG, Munich, Germany.
authors.forename: D
authors.initials: D
authors.lastname: Rüttinger
authors.affiliation: Department of Medicine (Cancer Research), West German Cancer Center, University Hospital Essen, Essen, Germany.
authors.forename: M
authors.initials: M
authors.lastname: Schuler
authors.affiliation: Clinical Development, Micromet AG, Munich, Germany. Electronic address: carsten.reinhardt@micromet.de.
authors.forename: C
authors.initials: C
authors.lastname: Reinhardt
authors.affiliation: Institut Jules Bordet, Unité Chemiothérapie, Université Libre de Bruxelles, Brussels, Belgium.
authors.forename: A
authors.initials: A
authors.lastname: Awada
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; D000951:Antigens, Neoplasm / Q000276:immunology*; D000970:Antineoplastic Agents / Q000008:administration & dosage / Q000009:adverse effects / Q000627:therapeutic use; D001943:Breast Neoplasms / Q000188:drug therapy* / Q000473:pathology; D015815:Cell Adhesion Molecules / Q000008:administration & dosage / Q000009:adverse effects / Q000276:immunology* / Q000627:therapeutic use*; D018450:Disease Progression; D018572:Disease-Free Survival; D004305:Dose-Response Relationship, Drug; D000071858:Epithelial Cell Adhesion Molecule; D005260:Female; D006801:Humans; D008875:Middle Aged; D009362:Neoplasm Metastasis; D016896:Treatment Outcome
chemical_list: D000911:Antibodies, Monoclonal; D061067:Antibodies, Monoclonal, Humanized; D000951:Antigens, Neoplasm; D000970:Antineoplastic Agents; D015815:Cell Adhesion Molecules; C499379:EPCAM protein, human; D000071858:Epithelial Cell Adhesion Molecule; C460839:adecatumumab