Soluble KIT correlates with clinical outcome in patients with metastatic breast cancer treated with sunitinib

Kiana Keyvanjah, Samuel E DePrimo, Charles S Harmon, Xin Huang, Kenneth A Kern, William Carley, Kiana Keyvanjah, Samuel E DePrimo, Charles S Harmon, Xin Huang, Kenneth A Kern, William Carley

Abstract

Background: Sunitinib inhibits vascular endothelial growth factor receptors (VEGFRs), platelet-derived growth factor receptors, and stem cell factor receptor (KIT). The ability of soluble (s)KIT, VEGF-A, sVEGFR-2, and sVEGFR-3 to predict clinical outcome was analyzed in 61 patients with previously treated metastatic breast cancer (MBC) in a phase II study of sunitinib monotherapy (ClinicalTrials.gov NCT00078000).

Methods: Plasma concentrations of soluble proteins were measured at baseline and during treatment with sunitinib 50 mg/day (4 weeks on treatment, 2 weeks off treatment). Baseline concentrations and maximal percent change during the first two treatment cycles were stratified by median values and evaluated for correlation with median time to tumor progression (TTP) and overall survival (OS). This latter fixed time period was chosen to avoid bias accruing from patients who were on study for longer periods of time.

Results: TTP was significantly longer in patients having median or higher maximal percent sKIT change compared with patients with less than the median change (21.7 vs. 7.9 weeks; p < 0.0001). Similarly, OS was significantly longer in patients having median or higher sKIT change versus less than the median change (53.7 vs. 25.7 weeks; p = 0.018). Significant prolongation of OS (62.6 vs. 32.3 weeks; p = 0.032), but not TTP, was observed in patients with a median or higher maximal percent VEGF-A change compared with less than the median change. Maximal percent change of sVEGFR-2 or sVEGFR-3 concentrations and baseline concentrations of all four proteins were not predictive of clinical outcome.

Conclusions: This exploratory analysis suggests that changes in sKIT and possibly VEGF-A early during sunitinib treatment may be predictive of clinical outcome in MBC.

Figures

Figure 1
Figure 1
Plasma protein concentrations in individual patients during treatment with sunitinib. (A) sKIT. (B) VEGF-A. (C) sVEGFR-2. (D) sVEGFR-3. sKIT, soluble KIT; sVEGFR, soluble vascular endothelial growth factor receptor; VEGF, vascular endothelial growth factor.
Figure 2
Figure 2
Maximal percent change in plasma protein concentration from C1D1 to C2D28 by patient. (A) sKIT. (B) VEGF-A. (C) sVEGFR-2. (D) sVEGFR-3. Light gray bars denote patients with triple-negative disease. Broken horizontal lines denote median values for each protein. C, cycle; D, day; sKIT, soluble KIT; sVEGFR, soluble vascular endothelial growth factor receptor; VEGF, vascular endothelial growth factor.
Figure 3
Figure 3
TTP and OS by median maximal percent change in plasma protein concentration through C2D28. (A) TTP by sKIT concentration. (B) OS by sKIT concentration. (C) TTP by VEGF-A concentration. (D) OS by VEGF-A concentration. C, cycle; D, day; OS, overall survival; sKIT, soluble KIT; TTP, time to tumor progression; VEGF, vascular endothelial growth factor.

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Source: PubMed

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