PKPD Modeling of VEGF, sVEGFR-2, sVEGFR-3, and sKIT as Predictors of Tumor Dynamics and Overall Survival Following Sunitinib Treatment in GIST
2013 (English)In: CPT: pharmacometrics & systems pharmacology, ISSN 2163-8306, Vol. 2, e84- p.Article in journal (Refereed) Published
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.
Place, publisher, year, edition, pages
2013. Vol. 2, e84- p.
Medical and Health Sciences
IdentifiersURN: urn:nbn:se:uu:diva-213434DOI: 10.1038/psp.2013.61PubMedID: 24257372OAI: oai:DiVA.org:uu-213434DiVA: diva2:682073