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 withadecatumumab 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.
RCT Entities:
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: Peter Kubatka; Sona Uramova; Martin Kello; Karol Kajo; Peter Kruzliak; Jan Mojzis; Desanka Vybohova; Marian Adamkov; Karina Jasek; Zora Lasabova; Pavol Zubor; Silvia Fialova; Svetlana Dokupilova; Peter Solar; Martin Pec; Katarina Adamicova; Jan Danko; Mariusz Adamek; Dietrich Busselberg Journal: J Cell Mol Med Date: 2017-05-19 Impact factor: 5.310
Authors: Tetsunari Hase; Mitsuo Sato; Kenya Yoshida; Luc Girard; Yoshihiro Takeyama; Mihoko Horio; Momen Elshazley; Tomoyo Oguri; Yoshitaka Sekido; David S Shames; Adi F Gazdar; John D Minna; Masashi Kondo; Yoshinori Hasegawa Journal: Cancer Sci Date: 2011-06-02 Impact factor: 6.716
Authors: Ranju Ralhan; Helen C-H He; Anthony K-C So; Satyendra C Tripathi; Manish Kumar; Md Raghibul Hasan; Jatinder Kaur; Lawrence Kashat; Christina MacMillan; Shyam Singh Chauhan; Jeremy L Freeman; Paul G Walfish Journal: PLoS One Date: 2010-11-30 Impact factor: 3.240
Authors: S Karabulut; F Tas; D Tastekin; M Karabulut; C T Yasasever; R Ciftci; M Güveli; M Fayda; S Vatansever; M Serilmez; R Disci; A Aydıner Journal: Tumour Biol Date: 2014-06-03