Prognostic and predictive value of VEGF, sVEGFR-2 and CEA in mCRC studies comparing cediranib, bevacizumab and chemotherapy

Jürgensmeier, Juliane M.; Schmoll, H.-J.; Robertson, Jane; Brooks, Laura; Taboada, Maria; Morgan, Shethah; Wilson, David M.; Hoff, Paulo M.

doi:10.1038/bjc.2013.79

Cited by 56 publications

(55 citation statements)

References 35 publications

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“…The connection between sVEGF and mortality in cancer has already been described in previous studies, and we can reconfirm these results (13,14).…”

Section: Svegf and The Pathogenesis Of Vte In Cancersupporting

confidence: 90%

“…TF activity has been shown to be increased more than 100-fold after the exposition to VEGF and TNFa (11). Elevated levels of VEGF are present in the bloodstream of patients with highly prothrombotic malignancies, such as ovarian and renal carcinomas (12), and have been reported to be associated with primary resistance to chemotherapy and increased mortality (13)(14)(15). Monocytes, endothelial cells, lymphocytes, and granulocytes also express VEGF on their surface (16).…”

Section: Introductionmentioning

confidence: 99%

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Soluble Vascular Endothelial Growth Factor (sVEGF) and the Risk of Venous Thromboembolism in Patients with Cancer: Results from the Vienna Cancer and Thrombosis Study (CATS)

Posch

Thaler

Zlabinger

et al. 2016

Clinical Cancer Research

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Purpose: Cancer patients are at an increased risk of venous thromboembolism (VTE). VEGF promotes the growth of highly thrombogenic tumor vessels. Here, we explored the utility of soluble plasma VEGF-A (sVEGF) as a biomarker for the prediction of VTE in patients with cancer.Experimental Design: Eight hundred four patients with newly diagnosed cancer or progression after remission were prospectively followed for 2 years until the occurrence of VTE or death [tumor sites:, myeloma and lymphoma (n ¼ 99), and others (n ¼ 48)]. Primary endpoint was symptomatic or fatal VTE. sVEGF was measured by immunoassay in baseline plasma.Results: Fifty-five patients developed VTE (6.8%) and 364 patients (45.3%) died. Five-hundred and forty-two (68.3%) participants had sVEGF levels above the detection limit of 0.5 pg/mL. The median sVEGF level (25th-75th percentile) was 8.1 pg/mL (0-17.7). The cumulative 2-year incidence of VTE was 10.2% [95% confidence interval (CI), 6.4-14.9] in patients with sVEGF greater than the 75th percentile of the sVEGF distribution (Q3, cutoff: 17.7 pg/mL), and 5.9% (95% CI, 4.2-7.9) in patients with lower levels (P ¼ 0.03). The corresponding 2-year risk of death was 52.8% (95% CI, 46.0-60.0) and 43.9% (95% CI, 40.0-48.0), respectively (P ¼ 0.02). In univariable time-to-VTE regression, elevated sVEGF was associated with VTE [subhazard ratio (SHR) per 10 pg/mL increase, 1.04; 95% CI,1.00-1.09; P ¼ 0.04)]. The association between sVEGF and risk of VTE prevailed after multivariable adjustment for high-risk tumor sites, age, gender, factor VIII, thrombin generation potential, and soluble P-Selectin (adjusted SHR, 1.04; 95% CI, 1.00-1.09, P ¼ 0.05).Conclusions: Elevated sVEGF is associated with an increased risk of VTE in patients with cancer. Clin Cancer Res; 22(1); 200-6. Ó2015 AACR.

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“…The connection between sVEGF and mortality in cancer has already been described in previous studies, and we can reconfirm these results (13,14).…”

Section: Svegf and The Pathogenesis Of Vte In Cancersupporting

confidence: 90%

Section: Introductionmentioning

confidence: 99%

Soluble Vascular Endothelial Growth Factor (sVEGF) and the Risk of Venous Thromboembolism in Patients with Cancer: Results from the Vienna Cancer and Thrombosis Study (CATS)

Posch

Thaler

Zlabinger

et al. 2016

Clinical Cancer Research

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“…VEGF and sVEGFR-2 were measured previously in plasma in a central laboratory (Labcorp, Research Triangle Park, NC, USA) using commercially available Quantikine ELISAs; CEA values were collected as per investigator's analysis at site (Jürgensmeier et al , 2013). Figure 1 shows the statistical analyses based on the data obtained from plasma for the primary data set and serum for the BDS, along with CEA obtained locally for the primary data set and centrally for the BDS.…”

Section: Resultsmentioning

confidence: 99%

Prognostic/predictive value of 207 serum factors in colorectal cancer treated with cediranib and/or chemotherapy

et al. 2013

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Background:The prognostic and predictive value of multiple serum biomarkers was evaluated using samples from a randomised phase III study (HORIZON II) investigating chemotherapy with or without cediranib in metastatic colorectal cancer (mCRC).Methods:Baseline levels of 207 protein markers were measured in serum samples from 582 HORIZON II (FOLFOX/XELOX plus cediranib 20 mg (n=330) or placebo (n=252)) patients. Median baseline values of each biomarker were used to categorise patients as high or low. Markers were then assessed for their association with efficacy, defined by progression-free survival (PFS) and overall survival (OS). A generalised boosted regression model identified markers of particular interest.Results:Correlation of protein levels with PFS and OS suggested that multiple factors had a prognostic value, independent of treatment arm, including IL-6, IL-8, C-reactive protein (CRP), ICAM-1 and carcinoembryonic antigen (CEA). Among the angiogenesis regulators, low levels of vascular endothelial growth factor (VEGF), VEGF-D, VEGFR-1, VEGFR-3, NRP1 and Tie-2 correlated with better outcome.Conclusion:This large data set generated using serum samples from mCRC patients treated with chemotherapy and VEGF inhibitors, defines baseline characteristics for 207 serum proteins. Multiple prognostic factors were identified that could be disease related or predict which patients derive most benefit from 5-fluorouracil (5-FU)-based chemotherapy, meriting further exploration in prospective studies.

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“…The CEA classification of high vs. low was somewhat arbitrarily derived as the above or below the study median value, questioning the use of this threshold in other populations, but the results were validated in an independent cohort. Arguing against the use of CEA, a similar unrelated retrospective analysis did not observe that CEA predicted response to either bevacizumab or cediranib [48]. Additional suggested predictive biomarkers for bevacizumab treatment response and/or efficacy include: level of tumor VEGF-A expression, germline genetic variations in pericyte maturation genes, PTEN loss, and levels of phosphorylated AMP-activated protein kinase (pAMPK) [49–53].…”

Section: Anti-angiogenic Therapymentioning

confidence: 99%

Molecular Markers Predictive of Chemotherapy Response in Colorectal Cancer

Shiovitz

Grady

2015

Curr Gastroenterol Rep

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Recognition of the molecular heterogeneity of colorectal cancer (CRC) has led to the classification of CRC based on a variety of clinical and molecular characteristics. Although the clinical significance of the majority of these molecular alterations is still being ascertained, it is widely anticipated that these characteristics will improve the accuracy of our ability to determine the prognosis and therapeutic response of CRC patients. A few of these markers, such as microsatellite instability and the CpG island methylator phenotype (CIMP), show promise as predictive markers for cytotoxic chemotherapy. KRAS is a validated biomarker for EGFR-targeted therapy, while NRAS and PI3KCA are evolving markers for targeted therapies. Multiple new actionable drug targets are being identified on a regular basis, but most are not ready for clinical use at this time. This review focuses on key molecular features of CRCs and the application of these molecular alterations as predictive biomarkers for CRC.

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Prognostic and predictive value of VEGF, sVEGFR-2 and CEA in mCRC studies comparing cediranib, bevacizumab and chemotherapy

Cited by 56 publications

References 35 publications

Soluble Vascular Endothelial Growth Factor (sVEGF) and the Risk of Venous Thromboembolism in Patients with Cancer: Results from the Vienna Cancer and Thrombosis Study (CATS)

Soluble Vascular Endothelial Growth Factor (sVEGF) and the Risk of Venous Thromboembolism in Patients with Cancer: Results from the Vienna Cancer and Thrombosis Study (CATS)

Prognostic/predictive value of 207 serum factors in colorectal cancer treated with cediranib and/or chemotherapy

Molecular Markers Predictive of Chemotherapy Response in Colorectal Cancer

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