Focal Irradiation and Systemic TGFß Blockade in Metastatic Breast Cancer.
Clin Cancer Res
; 24(11): 2493-2504, 2018 06 01.
Article
em En
| MEDLINE
| ID: mdl-29476019
ABSTRACT
Purpose:
This study examined the feasibility, efficacy (abscopal effect), and immune effects of TGFß blockade during radiotherapy in metastatic breast cancer patients.ExperimentalDesign:
Prospective randomized trial comparing two doses of TGFß blocking antibody fresolimumab. Metastatic breast cancer patients with at least three distinct metastatic sites whose tumor had progressed after at least one line of therapy were randomized to receive 1 or 10 mg/kg of fresolimumab, every 3 weeks for five cycles, with focal radiotherapy to a metastatic site at week 1 (three doses of 7.5 Gy), that could be repeated to a second lesion at week 7. Research bloods were drawn at baseline, week 2, 5, and 15 to isolate PBMCs, plasma, and serum.Results:
Twenty-three patients were randomized, median age 57 (range 35-77). Seven grade 3/4 adverse events occurred in 5 of 11 patients in the 1 mg/kg arm and in 2 of 12 patients in the 10 mg/kg arm, respectively. Response was limited to three stable disease. At a median follow up of 12 months, 20 of 23 patients are deceased. Patients receiving the 10 mg/kg had a significantly higher median overall survival than those receiving 1 mg/kg fresolimumab dose [hazard ratio 2.73 with 95% confidence interval (CI), 1.02-7.30; P = 0.039]. The higher dose correlated with improved peripheral blood mononuclear cell counts and a striking boost in the CD8 central memory pool.Conclusions:
TGFß blockade during radiotherapy was feasible and well tolerated. Patients receiving the higher fresolimumab dose had a favorable systemic immune response and experienced longer median overall survival than the lower dose group. Clin Cancer Res; 24(11); 2493-504. ©2018 AACR.
Texto completo:
1
Coleções:
01-internacional
Temas:
Geral
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Tipos_de_cancer
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Outros_tipos
Base de dados:
MEDLINE
Assunto principal:
Radioterapia
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Neoplasias da Mama
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Fator de Crescimento Transformador beta
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Antineoplásicos
Tipo de estudo:
Clinical_trials
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Etiology_studies
Limite:
Adult
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Aged
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Female
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Humans
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Middle aged
Idioma:
En
Revista:
Clin Cancer Res
Assunto da revista:
NEOPLASIAS
Ano de publicação:
2018
Tipo de documento:
Article