alexa Circulating levels of soluble KIT serve as a biomarker for clinical outcome in gastrointestinal stromal tumor patients receiving sunitinib following imatinib failure.
Genetics & Molecular Biology

Genetics & Molecular Biology

Journal of Molecular Biomarkers & Diagnosis

Author(s): Deprimo SE, Huang X, Blackstein ME, Garrett CR, Harmon CS,

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Abstract PURPOSE: To evaluate changes in circulating levels of soluble KIT (sKIT) extracellular domain as a potential biomarker for clinical outcome in gastrointestinal stromal tumor patients treated with the multitargeted tyrosine kinase inhibitor sunitinib following imatinib failure in a previously reported phase III study. EXPERIMENTAL DESIGN: Patients received sunitinib 50 mg/d (n = 243) or placebo (n = 118) daily in 6-week cycles (4 weeks on, 2 weeks off treatment). Plasma sKIT levels were sampled every 2 weeks in cycle 1 and on days 1 and 28 of subsequent cycles; analyzed by ELISA; and evaluated using Prentice criteria, Cox proportional hazards models, and proportion of treatment effect (PTE) analysis. RESULTS: From 4 weeks on treatment and onward, significant differences were shown between treatment groups (P < 0.0001) in sKIT level changes from baseline (median levels decreased with sunitinib and increased with placebo). Decreases in sKIT levels were a significant predictor of longer time to tumor progression (TTP). Patients with reduced levels at the end of cycle 2 had a median TTP of 34.3 weeks versus 16.0 weeks for patients with increased levels [hazard ratio, 0.71; 95\% confidence interval (95\% CI), 0.61-0.83; P < 0.0001], and changes in sKIT levels replaced treatment as a stronger predictor of TTP (PTE, 0.80; 95\% CI, 0.34-3.70), showing even greater surrogacy on cycle 3 day 1 (PTE, 0.98; 95\% CI, 0.39-3.40). CONCLUSIONS: The results suggest that circulating plasma sKIT levels seem to function as a surrogate marker for TTP in gastrointestinal stromal tumor patients. Additional studies are warranted to confirm and expand these findings.
This article was published in Clin Cancer Res and referenced in Journal of Molecular Biomarkers & Diagnosis

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