Prognostic and Predictive Biomarkers in Patients with Metastatic Colorectal Cancer Receiving Regorafenib.


Journal

Molecular cancer therapeutics
ISSN: 1538-8514
Titre abrégé: Mol Cancer Ther
Pays: United States
ID NLM: 101132535

Informations de publication

Date de publication:
10 2020
Historique:
received: 30 03 2020
revised: 08 06 2020
accepted: 20 07 2020
pubmed: 5 8 2020
medline: 7 8 2021
entrez: 5 8 2020
Statut: ppublish

Résumé

Regorafenib is a tyrosine kinase inhibitor approved by the FDA for the treatment of patients with chemotherapy refractory metastatic colorectal cancer (mCRC). Regorafenib inhibits signaling through multiple receptors associated with angiogenesis, metastasis, and tumor immunity. Here, we report biomarker results from LCCC1029, a randomized, placebo-controlled, phase II trial of chemotherapy ± regorafenib in patients with second-line mCRC. A panel of 20 soluble protein biomarkers (termed the Angiome) was assessed in the plasma of 149 patients from the LCCC1029 trial both at baseline and along the treatment continuum. Baseline protein levels were analyzed for prognostic and predictive value for progression-free survival (PFS) and overall survival (OS). Changes in protein levels during treatment were analyzed for potential pharmacodynamic effects. Six markers (HGF, IL6, PlGF, VEGF-R1, OPN, and IL6R) were found to be prognostic for PFS. Nine markers (IL6, TIMP-1, PlGF, VCAM-1, ICAM-1, OPN, TSP-2, HGF, and VEGF-R1) were prognostic for OS. Higher baseline levels of OPN (

Identifiants

pubmed: 32747417
pii: 1535-7163.MCT-20-0249
doi: 10.1158/1535-7163.MCT-20-0249
doi:

Substances chimiques

Biomarkers, Tumor 0
Phenylurea Compounds 0
Pyridines 0
regorafenib 24T2A1DOYB

Types de publication

Journal Article Research Support, Non-U.S. Gov't

Langues

eng

Sous-ensembles de citation

IM

Pagination

2146-2154

Informations de copyright

©2020 American Association for Cancer Research.

Auteurs

Yingmiao Liu (Y)

Department of Medicine, Duke University Medical Center, Durham, North Carolina.

Jing Lyu (J)

Duke Cancer Institute, Durham, North Carolina.

Kirsten Bell Burdett (K)

Duke Cancer Institute, Durham, North Carolina.

Alexander B Sibley (AB)

Duke Cancer Institute, Durham, North Carolina.

Ace J Hatch (AJ)

Department of Medicine, Duke University Medical Center, Durham, North Carolina.

Mark D Starr (MD)

Department of Medicine, Duke University Medical Center, Durham, North Carolina.

John C Brady (JC)

Department of Medicine, Duke University Medical Center, Durham, North Carolina.

Kelli Hammond (K)

The University of North Carolina at Chapel Hill, Chapel Hill, North Carolina.

Federica Marmorino (F)

Department of Translational Research and New Technologies in Medicine and Surgery, Unit of Medical Oncology, Azienda Ospedaliero- Universitaria Pisana, University of Pisa, Pisa, Italy.

Daniele Rossini (D)

Department of Translational Research and New Technologies in Medicine and Surgery, Unit of Medical Oncology, Azienda Ospedaliero- Universitaria Pisana, University of Pisa, Pisa, Italy.

Richard M Goldberg (RM)

West Virginia University Cancer Institute, Morgantown, West Virginia.

Alfredo Falcone (A)

Department of Translational Research and New Technologies in Medicine and Surgery, Unit of Medical Oncology, Azienda Ospedaliero- Universitaria Pisana, University of Pisa, Pisa, Italy.

Chiara Cremolini (C)

Department of Translational Research and New Technologies in Medicine and Surgery, Unit of Medical Oncology, Azienda Ospedaliero- Universitaria Pisana, University of Pisa, Pisa, Italy.

Kouros Owzar (K)

Duke Cancer Institute, Durham, North Carolina.
Duke Department of Biostatistics & Bioinformatics, Durham, North Carolina.

Anastasia Ivanova (A)

The University of North Carolina at Chapel Hill, Chapel Hill, North Carolina.

Dominic T Moore (DT)

The University of North Carolina at Chapel Hill, Chapel Hill, North Carolina.

Michael S Lee (MS)

The University of North Carolina at Chapel Hill, Chapel Hill, North Carolina.

Hanna K Sanoff (HK)

The University of North Carolina at Chapel Hill, Chapel Hill, North Carolina.

Federico Innocenti (F)

The University of North Carolina at Chapel Hill, Chapel Hill, North Carolina.

Andrew B Nixon (AB)

Department of Medicine, Duke University Medical Center, Durham, North Carolina. anixon@duke.edu.

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Classifications MeSH