Phase II trial of humanized anti-Lewis Y monoclonal antibody for advanced hormone receptor-positive breast cancer that progressed following endocrine therapy

OBJECTIVES: The Lewis-Y antigen is expressed in 44%-90% of breast cancers (BCs). The expression of the antigen in carcinoma tissue differs from that in normal tissues. This study aimed to evaluate the clinical benefit of the humanized anti-Lewis Y monoclonal antibody, hu3S193, in advanced hormone re...

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Detalhes bibliográficos
Autores: Testa, Laura, Mano, Max, Arai, Roberto Jun, Bonadio, Renata Colombo, Serrano, Sergio V., Zorzetto, Marina M Costa, Crocamo, Susanne, Smaletz, Oren, Freitas-Junior, Ruffo, Hoff, Paulo M.
Formato: artículo
Estado:Versión publicada
Fecha de publicación:2021
País:Brasil
Recursos:Universidade de São Paulo (USP)
Repositorio:Clinics
Idioma:inglés
OAI Identifier:oai:revistas.usp.br:article/212977
Acesso em linha:https://www.revistas.usp.br/clinics/article/view/212977
Access Level:acceso abierto
Palavra-chave:Breast Cancer
Metastatic
Anti-Lewis Y
Monoclonal Antibody
Targeted Therapy
Descrição
Resumo:OBJECTIVES: The Lewis-Y antigen is expressed in 44%-90% of breast cancers (BCs). The expression of the antigen in carcinoma tissue differs from that in normal tissues. This study aimed to evaluate the clinical benefit of the humanized anti-Lewis Y monoclonal antibody, hu3S193, in advanced hormone receptor-positive and Lewis Y-positive BC after administration of endocrine therapy (ET). METHODS: A single-arm phase II study was conducted in seven centers. Patients with advanced hormone receptor-positive BC who failed first-line ET were included. The inclusion criterion was the observation of tumoral expression of the Lewis Y antigen during immunohistochemistry. The treatment comprised hu3S193 antibody administration at weekly intravenous doses of 20 mg/m2 for 8-week cycles. The primary endpoint was the clinical benefit rate. ClinicalTrials.gov NCT01370239. RESULTS: The study stopped accrual following an unplanned interim analysis as the hu3S193 antibody lacked sufficient activity to justify continuation of the study. Twenty-two patients were enrolled, of whom 21 were included in the efficacy analysis. The clinical benefit rate was 19%, with four patients presenting with stable disease after 24 weeks. One patient with prolonged stable disease received medication for over 2 years. No partial or complete responses were observed. The median time to progression and overall survival was 5.4 and 37.5 months, respectively. CONCLUSIONS: The humanized anti-Lewis Y monoclonal antibody, hu3S193, exhibited insufficient activity in this cohort. However, the possibility of activity in a more strictly selected subgroup of patients with higher levels of Lewis Y tumoral expression cannot be overlooked.