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Conference Paper: Prognostic and predictive blood-based biomarkers in patients with advanced pancreatic cancer: Results from CALGB 80303

TitlePrognostic and predictive blood-based biomarkers in patients with advanced pancreatic cancer: Results from CALGB 80303
Authors
Issue Date2011
PublisherLippincott Williams & Wilkins.
Citation
The 2011 Annual Meeting of the American Society of Clinical Oncology (ASCO), Chicago, IL., 3-7 June 2011. In Journal of Clinical Oncology, 2011, v. 29 n. 15 suppl., abstract no. 10508 How to Cite?
AbstractBACKGROUND: CALGB 80303 was a phase III trial of 602 patients (pts) with locally advanced or metastatic pancreatic cancer (PC) comparing gemcitabine + bevacizumab (GB) vs. gemcitabine + placebo (GP). That study found no overall survival (OS) benefit from the addition of B. Blood samples were collected for prospective biomarker analyses. METHODS: Plasma samples were analyzed via a novel multiplex ELISA platform for >40 candidate factors related to tumor growth, angiogenesis, and inflammation. This platform was optimized for use in cancer patients. Baseline values were correlated with OS using univariate Cox proportional hazard regression models and multivariate Cox models with leave-one-out cross validation (LOOCV). Potential predictive markers were identified using a treatment by marker interaction term in the Cox model. RESULTS: 328 pts had baseline samples available. Univariate prognostic markers predicting OS identified within the GB and GP cohorts included: Ang2, CRP, ICAM-1, IGFBP-1, TSP-2 (all p<0.001). By multivariate analysis, these markers were significantly more prognostic than standard clinical factors, such as age, gender, extent of disease and performance status. LOOCV modeling yielded consistent multivariate prognostic signatures that differentiated patients with longer vs. shorter survival. The signature for the GB group consisted of IGFBP-1, IL-6, PDGF-AA, PDGF-BB, TSP-2; while the signature for the GP group consisted of CRP, IGFBP-1, PAI-1, PDGF-AA, PEDF (both p<0.0001). Three potential predictive markers of superior OS for GB vs. GP were identified: VEGF-D (p<0.01), SDF-1b (p<0.05), and Ang2 (p<0.05). Spearman's rank correlation coefficients suggested that many factors were co-regulated. CONCLUSIONS: This is one of the first phase III studies to report multiplex angiome profiling and it shows that tumor angiogenesis factors are highly prognostic in patients with PC. Several of these factors may define those pts more or less likely to benefit from the addition of B to G. This information should allow better stratification of patients with PC and may guide novel therapeutic interventions in PC and perhaps other cancers.
DescriptionThis journal suppl. entitled: ASCO Meeting Abstracts Part 1
Persistent Identifierhttp://hdl.handle.net/10722/195771
ISSN
2015 Impact Factor: 20.982
2015 SCImago Journal Rankings: 9.204

 

DC FieldValueLanguage
dc.contributor.authorNixon, ABen_US
dc.contributor.authorPang, HMHen_US
dc.contributor.authorStarr, Men_US
dc.contributor.authorHollis, Den_US
dc.contributor.authorFriedman, PNen_US
dc.contributor.authorBertagnolli, MMen_US
dc.contributor.authorKindler, HLen_US
dc.contributor.authorGoldberg, RMen_US
dc.contributor.authorVenook, APen_US
dc.contributor.authorHurwitz, Hen_US
dc.date.accessioned2014-03-10T04:52:54Z-
dc.date.available2014-03-10T04:52:54Z-
dc.date.issued2011en_US
dc.identifier.citationThe 2011 Annual Meeting of the American Society of Clinical Oncology (ASCO), Chicago, IL., 3-7 June 2011. In Journal of Clinical Oncology, 2011, v. 29 n. 15 suppl., abstract no. 10508en_US
dc.identifier.issn0732-183X-
dc.identifier.urihttp://hdl.handle.net/10722/195771-
dc.descriptionThis journal suppl. entitled: ASCO Meeting Abstracts Part 1-
dc.description.abstractBACKGROUND: CALGB 80303 was a phase III trial of 602 patients (pts) with locally advanced or metastatic pancreatic cancer (PC) comparing gemcitabine + bevacizumab (GB) vs. gemcitabine + placebo (GP). That study found no overall survival (OS) benefit from the addition of B. Blood samples were collected for prospective biomarker analyses. METHODS: Plasma samples were analyzed via a novel multiplex ELISA platform for >40 candidate factors related to tumor growth, angiogenesis, and inflammation. This platform was optimized for use in cancer patients. Baseline values were correlated with OS using univariate Cox proportional hazard regression models and multivariate Cox models with leave-one-out cross validation (LOOCV). Potential predictive markers were identified using a treatment by marker interaction term in the Cox model. RESULTS: 328 pts had baseline samples available. Univariate prognostic markers predicting OS identified within the GB and GP cohorts included: Ang2, CRP, ICAM-1, IGFBP-1, TSP-2 (all p<0.001). By multivariate analysis, these markers were significantly more prognostic than standard clinical factors, such as age, gender, extent of disease and performance status. LOOCV modeling yielded consistent multivariate prognostic signatures that differentiated patients with longer vs. shorter survival. The signature for the GB group consisted of IGFBP-1, IL-6, PDGF-AA, PDGF-BB, TSP-2; while the signature for the GP group consisted of CRP, IGFBP-1, PAI-1, PDGF-AA, PEDF (both p<0.0001). Three potential predictive markers of superior OS for GB vs. GP were identified: VEGF-D (p<0.01), SDF-1b (p<0.05), and Ang2 (p<0.05). Spearman's rank correlation coefficients suggested that many factors were co-regulated. CONCLUSIONS: This is one of the first phase III studies to report multiplex angiome profiling and it shows that tumor angiogenesis factors are highly prognostic in patients with PC. Several of these factors may define those pts more or less likely to benefit from the addition of B to G. This information should allow better stratification of patients with PC and may guide novel therapeutic interventions in PC and perhaps other cancers.-
dc.languageengen_US
dc.publisherLippincott Williams & Wilkins.-
dc.relation.ispartofJournal of Clinical Oncologyen_US
dc.titlePrognostic and predictive blood-based biomarkers in patients with advanced pancreatic cancer: Results from CALGB 80303en_US
dc.typeConference_Paperen_US
dc.identifier.emailPang, HMH: herbpang@hku.hken_US
dc.identifier.authorityPang, HMH=rp01857en_US
dc.identifier.volume29en_US
dc.identifier.issue15 suppl. (May 20 Supplement)-
dc.publisher.placeUnited States-

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