Serum osteopontin predicts the response to atezolizumab plus bevacizumab in patients with hepatocellular carcinoma.
Angiopoietin-2
Immune checkpoint inhibitor
Macrophage
PD-L1
VEGF
Journal
Journal of gastroenterology
ISSN: 1435-5922
Titre abrégé: J Gastroenterol
Pays: Japan
ID NLM: 9430794
Informations de publication
Date de publication:
06 2023
06 2023
Historique:
received:
26
12
2022
accepted:
18
03
2023
medline:
22
5
2023
pubmed:
30
3
2023
entrez:
29
3
2023
Statut:
ppublish
Résumé
Combination therapy with anti-programmed death-ligand 1 and anti-vascular endothelial growth factor (VEGF) antibodies has become the standard treatment for un-resectable hepatocellular carcinoma (uHCC). We aimed to identify predictive circulating biomarkers for the outcome/response of the combination therapy in uHCC patients. This prospective multicenter study enrolled 70 patients with uHCC who received atezolizumab and bevacizumab (Atez/Bev). We evaluated 47 circulating proteins in sera before and after 1 and 6 weeks of Atez/Bev therapy by multiplex bead-based immunoassay and ELISA. As controls, we analyzed the sera from 62 uHCC patients before treatment of lenvatinib (LEN) and healthy volunteers (HVs). The disease control rate was 77.1%. Median progression-free survival (PFS) was 5.7 months (95% confidence interval [CI] = 3.8-9.5). The pretreatment levels of osteopontin (OPN), angiopoietin-2, VEGF, S100-calcium-binding protein A8/S100-calcium-binding protein A9, soluble programmed cell death-1, soluble CD163, and 14 cytokines/chemokines were higher in patients with uHCC than in HVs. Among these, pretreatment OPN levels were higher in PD group than in non-PD group for Atez/Bev. The PD rate was higher in high OPN group than in low OPN group. Multivariate analysis identified high pretreatment OPN and high α-fetoprotein levels as independent predictors of PD. In the sub-analysis of Child-Pugh class A patients, PFS was also shorter in the high OPN group than in the low OPN group. Pretreatment OPN level was not associated with treatment response for LEN. High serum OPN levels were associated with poor response to Atez/Bev in patients with uHCC.
Sections du résumé
BACKGROUND
Combination therapy with anti-programmed death-ligand 1 and anti-vascular endothelial growth factor (VEGF) antibodies has become the standard treatment for un-resectable hepatocellular carcinoma (uHCC). We aimed to identify predictive circulating biomarkers for the outcome/response of the combination therapy in uHCC patients.
METHODS
This prospective multicenter study enrolled 70 patients with uHCC who received atezolizumab and bevacizumab (Atez/Bev). We evaluated 47 circulating proteins in sera before and after 1 and 6 weeks of Atez/Bev therapy by multiplex bead-based immunoassay and ELISA. As controls, we analyzed the sera from 62 uHCC patients before treatment of lenvatinib (LEN) and healthy volunteers (HVs).
RESULTS
The disease control rate was 77.1%. Median progression-free survival (PFS) was 5.7 months (95% confidence interval [CI] = 3.8-9.5). The pretreatment levels of osteopontin (OPN), angiopoietin-2, VEGF, S100-calcium-binding protein A8/S100-calcium-binding protein A9, soluble programmed cell death-1, soluble CD163, and 14 cytokines/chemokines were higher in patients with uHCC than in HVs. Among these, pretreatment OPN levels were higher in PD group than in non-PD group for Atez/Bev. The PD rate was higher in high OPN group than in low OPN group. Multivariate analysis identified high pretreatment OPN and high α-fetoprotein levels as independent predictors of PD. In the sub-analysis of Child-Pugh class A patients, PFS was also shorter in the high OPN group than in the low OPN group. Pretreatment OPN level was not associated with treatment response for LEN.
CONCLUSION
High serum OPN levels were associated with poor response to Atez/Bev in patients with uHCC.
Identifiants
pubmed: 36991155
doi: 10.1007/s00535-023-01985-w
pii: 10.1007/s00535-023-01985-w
doi:
Substances chimiques
Bevacizumab
2S9ZZM9Q9V
atezolizumab
52CMI0WC3Y
Osteopontin
106441-73-0
Vascular Endothelial Growth Factor A
0
Calcium-Binding Proteins
0
Types de publication
Multicenter Study
Journal Article
Research Support, Non-U.S. Gov't
Langues
eng
Sous-ensembles de citation
IM
Pagination
565-574Subventions
Organisme : AMED
ID : 22fk0210110
Organisme : AMED
ID : 22fk0210094
Organisme : Grants-in-Aid for Scientific Research
ID : 21K08020
Informations de copyright
© 2023. Japanese Society of Gastroenterology.
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