An open-label, randomized phase II study of adecatumumab, a fully human anti-EpCAM antibody, as monotherapy in patients with metastatic breast cancer.
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.
Schmidt
M
M
Department of Obstetrics and Gynecology, Johannes Gutenberg University, Mainz.
Scheulen
M E
ME
Department of Medicine (Cancer Research), West German Cancer Center, University Hospital Essen, Essen, Germany.
Dittrich
C
C
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.
Obrist
P
P
Department of Pathology, St Vinzenz Hospital, Zams, Austria.
Marschner
N
N
Practice for Oncology and Hematology, Freiburg, Germany.
Dirix
L
L
Medical Oncology Unit, Oncologisch Centrum Sint-Augustinus, Antwerp, Belgium.
Schmidt
M
M
Clinical Development, Micromet AG, Munich, Germany.
Rüttinger
D
D
Clinical Development, Micromet AG, Munich, Germany.
Schuler
M
M
Department of Medicine (Cancer Research), West German Cancer Center, University Hospital Essen, Essen, Germany.
Reinhardt
C
C
Clinical Development, Micromet AG, Munich, Germany. Electronic address: carsten.reinhardt@micromet.de.
Awada
A
A
Institut Jules Bordet, Unité Chemiothérapie, Université Libre de Bruxelles, Brussels, Belgium.
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
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