Abstract
Purpose: Lewis Y antigen is expressed in 44 to 90% of breast cancer. The expression of the antigen in carcinoma tissue is different from what occurs in normal tissue. The objective of the present study was to evaluate the clinical benefit of the humanized anti-Lewis Y monoclonal antibody, hu3S193, in advanced hormone receptor-positive and Lewis Y-positive breast cancer, after progression on endocrine therapy.Methods: A single-arm phase II study was conducted in 7 centers. Patients with advanced hormone receptor-positive breast cancer who had failed previous first-line endocrine therapy were included. All patients were required to present tumoral expression of Lewis Y antigen by immunohistochemistry. Treatment consisted of hu3S193 antibody at intravenous doses of 20 mg/m2 weekly given at 8-week cycles. The primary endpoint was clinical benefit rate. Results: The study stopped accrual after an unplanned interim analysis since the hu3S193 antibody lacked sufficient activity to justify the study continuation. Twenty-two patients were enrolled; 21 were included in the efficacy analysis. The clinical benefit rate was 19%, with four patients presenting stable disease confirmed after 24 weeks. One patient received the medication for more than 2 years, with prolonged stable disease. No partial or complete responses were observed. Median time to progression and overall survival were 5.4 and 37.5 months, respectively. Conclusions: The humanized anti-Lewis Y monoclonal antibody, hu3S193, showed insufficient activity in this cohort. However, we cannot rule out the possibility of activity in a more strictly selected subgroup of patients with higher levels of Lewis Y tumoral expression.Trial registration: Clinicaltrials.gov, NCT01370239. Registered 9 June 2011, https://clinicaltrials.gov/ct2/show/NCT01370239
A Phase I Biodistribution and Pharmacokinetic Trial of Humanized Monoclonal Antibody Hu3s193 in Patients with Advanced Epithelial Cancers that Express the Lewis-Y Antigen
