Title: Circulating levels of soluble KIT serve as a biomarker for clinical outcome in gastrointestinal stromal tumor patients receiving sunitinib following imatinib failure
Authors: Deprimo, Samuel E ×
Huang, Xin
Blackstein, Martin E
Garrett, Christopher R
Harmon, Charles S
Schöffski, Patrick
Shah, Manisha H
Verweij, Jaap
Baum, Charles M
Demetri, George D #
Issue Date: Sep-2009
Series Title: Clinical Cancer Research vol:15 issue:18 pages:5869-5877
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.
ISSN: 1078-0432
Publication status: published
KU Leuven publication type: IT
Appears in Collections:Laboratory of Experimental Oncology
× corresponding author
# (joint) last author

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