Biomarkers and overall survival in patients with advanced hepatocellular carcinoma treated with TGF-ßRI inhibitor galunisertib.
PLoS One
; 15(3): e0222259, 2020.
Article
em En
| MEDLINE
| ID: mdl-32210440
ABSTRACT
BACKGROUND:
Transforming growth factor beta (TGF-ß) signalling is involved in the development of hepatocellular carcinoma (HCC). We followed changes in biomarkers during treatment of patients with HCC with the TGF-ßRI/ALK5 inhibitor galunisertib.METHODS:
This phase 2 study (NCT01246986) enrolled second-line patients with advanced HCC into one of two cohorts of baseline serum alpha-fetoprotein (AFP) Part A (AFP ≥1.5x ULN) or Part B (AFP <1.5x ULN). Baseline and postbaseline levels of AFP, TGF-ß1, E-cadherin, selected miRNAs, and other plasma proteins were monitored.RESULTS:
The study enrolled 149 patients (Part A, 109; Part B, 40). Median OS was 7.3 months in Part A and 16.8 months in Part B. Baseline AFP, TGF-ß1, E-cadherin, and an additional 16 plasma proteins (such as M-CSF, IL-6, ErbB3, ANG-2, neuropilin-1, MIP-3 alpha, KIM-1, uPA, IL-8, TIMP-1, ICAM-1, Apo A-1, CA-125, osteopontin, tetranectin, and IGFBP-1) were found to correlate with OS. In addition, a range of miRs were found to be associated with OS. In AFP responders (21% of patients in Part A with decrease of >20% from baseline) versus non-responders, median OS was 21.5 months versus 6.8 months (p = 0.0015). In TGF-ß1 responders (51% of all patients) versus non-responders, median OS was 11.2 months versus 5.3 months (p = 0.0036).CONCLUSIONS:
Consistent with previous findings, both baseline levels and changes from baseline of circulating AFP and TGF-ß1 function as prognostic indicators of survival. Future trials are needed to confirm and extend these results.
Texto completo:
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Base de dados:
MEDLINE
Assunto principal:
Pirazóis
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Quinolinas
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Carcinoma Hepatocelular
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Receptor do Fator de Crescimento Transformador beta Tipo I
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Neoplasias Hepáticas
Tipo de estudo:
Clinical_trials
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Etiology_studies
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Incidence_studies
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Observational_studies
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Prognostic_studies
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Risk_factors_studies
Limite:
Adult
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Aged
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Aged80
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Female
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Humans
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Male
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Middle aged
Idioma:
En
Ano de publicação:
2020
Tipo de documento:
Article