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DDMODEL00000048: Overall Survival model for Sunitinib Treatment in GIST

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Short description:
A parametric time-to-event model, developed to explore the relationships between the four biomarkers, tumor size, and overall survival following sunitinib treatment in GIST.
Original code
  • PKPD Modeling of VEGF, sVEGFR-2, sVEGFR-3, and sKIT as Predictors of Tumor Dynamics and Overall Survival Following Sunitinib Treatment in GIST.
  • Hansson EK, Amantea MA, Westwood P, Milligan PA, Houk BE, French J, Karlsson MO, Friberg LE
  • CPT: pharmacometrics & systems pharmacology, 1/2013, Volume 2, pages: e84
  • Department of Pharmaceutical Biosciences, Uppsala University, Uppsala, Sweden.
  • The predictive value of longitudinal biomarker data (vascular endothelial growth factor (VEGF), soluble VEGF receptor (sVEGFR)-2, sVEGFR-3, and soluble stem cell factor receptor (sKIT)) for tumor response and survival was assessed based on data from 303 patients with imatinib-resistant gastrointestinal stromal tumors (GIST) receiving sunitinib and/or placebo treatment. The longitudinal tumor size data were well characterized by a tumor growth inhibition model, which included, as significant descriptors of tumor size change, the model-predicted relative changes from baseline over time for sKIT (most significant) and sVEGFR-3, in addition to sunitinib exposure. Survival time was best described by a parametric time-to-event model with baseline tumor size and relative change in sVEGFR-3 over time as predictive factors. Based on the proposed modeling framework to link longitudinal biomarker data with overall survival using pharmacokinetic-pharmacodynamic models, sVEGFR-3 demonstrated the greatest predictive potential for overall survival following sunitinib treatment in GIST.CPT: Pharmacometrics & Systems Pharmacology (2013) 2, e84; doi:10.1038/psp.2013.61; advance online publication 20 November 2013.
Sreenath M Krishnan
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  • Model owner: Sreenath M Krishnan
  • Submitted: Dec 15, 2015 12:44:23 PM
  • Last Modified: Jun 3, 2016 12:44:32 PM
Revisions
  • Version: 13 public model Download this version
    • Submitted on: Jun 3, 2016 12:44:32 PM
    • Submitted by: Sreenath M Krishnan
    • With comment: Updated model annotations.
  • Version: 12 public model Download this version
    • Submitted on: Jun 3, 2016 11:17:59 AM
    • Submitted by: Sreenath M Krishnan
    • With comment: Updated model annotations.
  • Version: 11 public model Download this version
    • Submitted on: Dec 15, 2015 12:44:23 PM
    • Submitted by: Sreenath M Krishnan
    • With comment: Edited model metadata online.
 
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