Phase IB study of the EpCAM antibody adecatumumab combined with docetaxel in patients with EpCAM-positive relapsed or refractory advanced-stage breast cancer

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 antibod...

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Veröffentlicht in:Annals of oncology 2012-09, Vol.23 (9), p.2306-2313
Hauptverfasser: Schmidt, M., Rüttinger, D., Sebastian, M., Hanusch, C.A., Marschner, N., Baeuerle, P.A., Wolf, A., Göppel, G., Oruzio, D., Schlimok, G., Steger, G.G., Wolf, C., Eiermann, W., Lang, A., Schuler, M.
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Sprache:eng
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Zusammenfassung: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. 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/m2 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. 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/m2 q3w and 360 mg/m2 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. Combination therapy of adecatumumab and docetaxel is safe, feasible, and potentially active in heavily pretreated advanced-stage breast cancer.
ISSN:0923-7534
1569-8041
DOI:10.1093/annonc/mdr625