A systematic review of predictive and prognostic biomarkers for VEGF-targeted therapy in renal cell carcinoma Journal Article


Authors: Funakoshi, T.; Lee, C. H.; Hsieh, J. J.
Article Title: A systematic review of predictive and prognostic biomarkers for VEGF-targeted therapy in renal cell carcinoma
Abstract: Background: Vascular endothelial growth factor (VEGF)-targeted therapy is the currently standard treatment for advanced and metastatic renal cell carcinoma (RCC). Multiple candidate predictive and prognostic biomarkers have been evaluated. We performed a systematic review and graded the available evidence on the biomarkers for VEGF-targeted therapy in RCC. Methods: We conducted an independent review of PubMed and ASCO databases up to August 2013. Studies were included if biomarkers obtained from metastatic clear-cell RCC patients treated with the FDA-approved VEGF-targeted therapy were assessed for their correlation with clinical outcomes. We graded the studies and determined the Level-of-evidence for each biomarker using a previously published framework. Results: A total of 50 articles were selected for this review. Seven studies assessed the predictive value of biomarkers using the archived specimens from randomized controlled trials. Five predictive biomarkers, such as VEGF, interleukin (IL)-6, hepatocyte growth factor (HGF), osteopontin, single nucleotide polymorphisms in IL-8, satisfied Level II evidence. IL-6 is the most corroborated predictive biomarker based on its consistent predictive value in two different trials. The prognostic value of biomarkers was assessed in 48 studies using the archived specimens from clinical trials, prospective and retrospective observational registries. Three biomarkers, including IL-8, HGF and osteopontin, satisfied Level I evidence for PFS. Conclusion: Though several promising predictive biomarkers for VEGF-targeted therapy have been found, none of them has satisfied the determination of Level I evidence. A more focused development of biomarkers with prospective assessment in clinical trials and clear intent of use in clinical practice is needed. © 2013 Elsevier Ltd.
Keywords: epidermal growth factor; protein kinase b; vasculotropin; vasculotropin receptor 3; cancer survival; protein expression; protein phosphorylation; unclassified drug; overall survival; single nucleotide polymorphism; review; evidence based medicine; biomarkers; biological marker; protein blood level; platelet derived growth factor alpha receptor; progression free survival; interleukin 5; interleukin 8; vasculotropin receptor 2; kidney carcinoma; vasculotropin c; scatter factor; regulatory t lymphocyte; tumor necrosis factor alpha; systematic review; phosphatidylinositol 3,4,5 trisphosphate 3 phosphatase; vasculotropin a; pazopanib; interleukin 6; transforming growth factor beta1; hypoxia inducible factor 1alpha; fibroblast growth factor receptor 2; predictive value; colony stimulating factor 1; endothelial leukocyte adhesion molecule 1; tissue inhibitor of metalloproteinase 1; platelet derived growth factor beta receptor; programmed death 1 ligand 1; stromal cell derived factor 1; randomized controlled trial (topic); phase 2 clinical trial (topic); phase 3 clinical trial (topic); metastatic renal cell carcinoma; chemokine receptor cxcr4; osteopontin; protein s6; alpha interferon receptor; cancer prognosis; human; vascular endothelial growth factor-targeted therapy; interferon alpha receptor 2; myeloid dendritic cell
Journal Title: Cancer Treatment Reviews
Volume: 40
Issue: 4
ISSN: 0305-7372
Publisher: Elsevier Inc.  
Date Published: 2014-05-01
Start Page: 533
End Page: 547
Language: English
DOI: 10.1016/j.ctrv.2013.11.008
PROVIDER: scopus
DOI/URL:
Notes: Export Date: 2 April 2014 -- CODEN: CTRED -- Source: Scopus
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  1. James J Hsieh
    125 Hsieh
  2. Chung-Han   Lee
    157 Lee