Soluble KIT correlates with clinical outcome in patients with metastatic breast cancer treated with sunitinib.
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.
Pfizer Oncology, La Jolla, CA, USA. kkeyvanj@gmail.com
Kiana
K
Keyvanjah
Samuel E
SE
DePrimo
Charles S
CS
Harmon
Xin
X
Huang
Kenneth A
KA
Kern
William
W
Carley
D000328:Adult; D000368:Aged; D000970:Antineoplastic Agents / Q000627:therapeutic use*; D014408:Biomarkers, Tumor / Q000097:blood*; D001943:Breast Neoplasms / Q000097:blood / Q000188:drug therapy* / Q000473:pathology; D005260:Female; D006801:Humans; D007211:Indoles / Q000627:therapeutic use*; D008875:Middle Aged; D009362:Neoplasm Metastasis; D019009:Proto-Oncogene Proteins c-kit / Q000097:blood*; D011758:Pyrroles / Q000627:therapeutic use*; D000077210:Sunitinib; D016896:Treatment Outcome
D000970:Antineoplastic Agents; D014408:Biomarkers, Tumor; D007211:Indoles; D011758:Pyrroles; D019009:Proto-Oncogene Proteins c-kit; D000077210:Sunitinib