title: Phase IB study of the EpCAM antibody adecatumumab combined with docetaxel in patients with EpCAM-positive relapsed or refractory advanced-stage breast cancer.
abstract: BACKGROUND
  Targeted therapy options in HER2-negative breast cancer are limited. This open-label, multicenter phase IB dose-escalation trial was conducted to determine safety, tolerability, and antitumor activity of a combination of docetaxel (Taxotere) and increasing doses of adecatumumab, a human IgG1 antibody targeting epithelial cell adhesion molecule (EpCAM), in EpCAM-positive relapsed or primary refractory advanced-stage breast cancer.
  
  
  METHODS
  Patients pretreated with up to four prior chemotherapy regimens received increasing adecatumumab doses either every 3 weeks (q3w) or weekly (qw) combined with docetaxel (100 mg/m(2) q3w). Primary end points were safety and tolerability. Antitumor activity was evaluated according to RECIST. Clinical benefit was defined as complete or partial response or stable disease for ≥24 weeks.
  
  
  RESULTS
  Thirty-one evaluable patients were treated. Most adverse events were mild to moderate in severity. Neutropenia, leukocytopenia, lymphopenia, and diarrhea (dose-limiting) were the most frequent toxic effects. Maximum tolerated doses of adecatumumab given in combination with docetaxel were 550 mg/m(2) q3w and 360 mg/m(2) qw. Clinical benefit was observed in 44% of patients treated with q3w adecatumumab and docetaxel, increasing to 63% in patients with high EpCAM-expressing tumors.
  
  
  CONCLUSIONS
  Combination therapy of adecatumumab and docetaxel is safe, feasible, and potentially active in heavily pretreated advanced-stage breast cancer.
authors.affiliation: Department of Obstetrics and Gynecology, University Medical Center of the Johannes Gutenberg University Mainz, Mainz, Germany.
authors.forename: M
authors.initials: M
authors.lastname: Schmidt
authors.affiliation: Micromet, Inc., Bethesda, USA; Micromet AG, Munich.
authors.forename: D
authors.initials: D
authors.lastname: Rüttinger
authors.affiliation: Department of Internal Medicine III, University Medical Center of the Johannes Gutenberg University Mainz, Mainz.
authors.forename: M
authors.initials: M
authors.lastname: Sebastian
authors.affiliation: Gynecological Hospital Red Cross, Munich.
authors.forename: C A
authors.initials: CA
authors.lastname: Hanusch
authors.affiliation: Practice for Oncology and Hematology, Freiburg.
authors.forename: N
authors.initials: N
authors.lastname: Marschner
authors.affiliation: Micromet, Inc., Bethesda, USA; Micromet AG, Munich.
authors.forename: P A
authors.initials: PA
authors.lastname: Baeuerle
authors.affiliation: Micromet, Inc., Bethesda, USA; Micromet AG, Munich.
authors.forename: A
authors.initials: A
authors.lastname: Wolf
authors.affiliation: Micromet, Inc., Bethesda, USA; Micromet AG, Munich.
authors.forename: G
authors.initials: G
authors.lastname: Göppel
authors.affiliation: Hospital Augsburg, II. Medical Center, Augsburg, Germany.
authors.forename: D
authors.initials: D
authors.lastname: Oruzio
authors.affiliation: Hospital Augsburg, II. Medical Center, Augsburg, Germany.
authors.forename: G
authors.initials: G
authors.lastname: Schlimok
authors.affiliation: Medical University Vienna, Department of Oncology, Vienna, Austria.
authors.forename: G G
authors.initials: GG
authors.lastname: Steger
authors.affiliation: Cooperative Breast Center, Ulm, Germany.
authors.forename: C
authors.initials: C
authors.lastname: Wolf
authors.affiliation: Gynecological Hospital Red Cross, Munich.
authors.forename: W
authors.initials: W
authors.lastname: Eiermann
authors.affiliation: State Hospital Feldkirch at State Hospital Rankweil, Rankweil, Austria.
authors.forename: A
authors.initials: A
authors.lastname: Lang
authors.affiliation: Department of Medical Oncology, West German Cancer Center, University Duisburg-Essen, Essen, Germany. Electronic address: martin.schuler@uk-essen.de.
authors.forename: M
authors.initials: M
authors.lastname: Schuler
mesh_terms: D000328:Adult; D000368:Aged; D000911:Antibodies, Monoclonal / Q000008:administration & dosage; D061067:Antibodies, Monoclonal, Humanized; D000951:Antigens, Neoplasm / Q000378:metabolism*; D000971:Antineoplastic Combined Chemotherapy Protocols / Q000009:adverse effects / Q000493:pharmacokinetics / Q000627:therapeutic use*; D001943:Breast Neoplasms / Q000188:drug therapy* / Q000378:metabolism / Q000473:pathology; D015815:Cell Adhesion Molecules / Q000008:administration & dosage / Q000378:metabolism*; D000077143:Docetaxel; D004334:Drug Administration Schedule; D019008:Drug Resistance, Neoplasm; D000071858:Epithelial Cell Adhesion Molecule; D005260:Female; D006801:Humans; D007960:Leukocyte Disorders / Q000139:chemically induced; D008113:Liver Neoplasms / Q000188:drug therapy* / Q000378:metabolism / Q000556:secondary; D008875:Middle Aged; D009364:Neoplasm Recurrence, Local / Q000188:drug therapy* / Q000378:metabolism / Q000473:pathology; D043823:Taxoids / Q000008:administration & dosage; D016896:Treatment Outcome
chemical_list: D000911:Antibodies, Monoclonal; D061067:Antibodies, Monoclonal, Humanized; D000951:Antigens, Neoplasm; D015815:Cell Adhesion Molecules; C499379:EPCAM protein, human; D000071858:Epithelial Cell Adhesion Molecule; D043823:Taxoids; C460839:adecatumumab; D000077143:Docetaxel