Safety and immunogenicity of neoadjuvant treatment using WT1-immunotherapeutic in combination with standard therapy in patients with WT1-positive Stage II/III breast cancer: a randomized Phase I study.
Breast Cancer Res Treat
; 162(3): 479-488, 2017 04.
Article
em En
| MEDLINE
| ID: mdl-28176175
ABSTRACT
PURPOSE:
This Phase I, multicenter, randomized study (ClinicalTrials.gov NCT01220128) evaluated the safety and immunogenicity of recombinant Wilms' tumor 1 (WT1) protein combined with the immunostimulant AS15 (WT1-immunotherapeutic) as neoadjuvant therapy administered concurrently with standard treatments in WT1-positive breast cancer patients.METHODS:
Patients were treated in 4 cohorts according to neoadjuvant treatment (A post-menopausal, hormone receptor [HR]-positive patients receiving aromatase inhibitors; B patients receiving chemotherapy; C HER2-overexpressing patients on trastuzumab-chemotherapy combination; D HR-positive/HER2-negative patients on chemotherapy). Patients (cohorts A-C) were randomized (21) to receive 6 or 8 doses of WT1-immunotherapeutic or placebo together with standard neoadjuvant treatment in a double-blind manner; cohort D patients received WT1-immunotherapeutic in an open manner. Safety was assessed throughout the study. WT1-specific antibodies were assessed pre- and post-vaccination.RESULTS:
Sixty-two patients were randomized; 60 received ≥ one dose of WT1-immunotherapeutic. Two severe toxicities were reported diarrhea (cohort C; also reported as a grade 3 serious adverse event) and decreased left ventricular ejection fraction (cohort B; also reported as a grade 2 adverse event). Post-dose 4 of WT1-immunotherapeutic, 10/10 patients from cohort A, 0/8 patients from cohort B, 6/11 patients from cohort C, and 2/3 patients from cohort D were humoral responders. The sponsor elected to close the trial prematurely.CONCLUSIONS:
Concurrent administration of WT1-immunotherapeutic and standard neoadjuvant therapy was well tolerated and induced WT1-specific antibodies in patients receiving neoadjuvant aromatase inhibitors. In patients on neoadjuvant chemotherapy or trastuzumab-chemotherapy combination, the humoral response was impaired or blunted, likely due to either co-administration of corticosteroids and/or the chemotherapies themselves.Palavras-chave
Texto completo:
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Coleções:
01-internacional
Base de dados:
MEDLINE
Assunto principal:
Proteínas Recombinantes
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Neoplasias da Mama
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Protocolos de Quimioterapia Combinada Antineoplásica
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Vacinas Anticâncer
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Proteínas WT1
Tipo de estudo:
Clinical_trials
Limite:
Female
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Humans
Idioma:
En
Revista:
Breast Cancer Res Treat
Ano de publicação:
2017
Tipo de documento:
Article
País de afiliação:
Irlanda