OS according to baseline STC1 plasma levels (optimized cut-off*) in patients with chemorefractory mCRC in the CORRECT study. A, Overall cohort (N = 646). B, Regorafenib cohort (n = 435). C, Placebo cohort (n = 211). *Optimized STC1 plasma levels: STC1 low: <1,436.87 pg/mL; STC1 high: ≥1,436.87 pg/mL.
ARTICLE ABSTRACT
Biomarkers for antiangiogenic drugs in chemorefractory metastatic colorectal cancer (mCRC) are lacking. We investigated the relationship between stanniocalcin 1 (STC1) and outcomes in patients treated with regorafenib in the TEXCAN and CORRECT trials. Baseline plasma STC1 protein levels were measured by ELISA from patients with chemorefractory mCRC enrolled in TEXCAN (regorafenib n = 48) and CORRECT (placebo n = 211; regorafenib n = 435). The relationship between STC1 levels and overall survival (OS) was assessed using a Cox proportional hazards model. The median STC1 value was increased in patients with chemorefractory mCRC (1,211 pg/mL) compared with previously untreated patients (215 pg/mL). Using an optimized cut-off, STC1 was prognostic for OS [HR = 2.12, 95% confidence interval (CI), 1.79–2.50; P < 0.001], with a median OS of 7.63 months in the STC1-low group (<1,436.87 pg/mL; n = 400) and 3.81 months in the STC1-high group (≥1,436.87 pg/mL; n = 246). The interaction P value of lactate dehydrogenase and treatment revealed no predictive effect of lactate dehydrogenase levels on OS in terms of regorafenib (P = 0.598). A predictive analysis suggested a significant association between STC1 and regorafenib for OS (interaction P = 0.049). The median OS with regorafenib versus placebo was 8.32 versus 6.54 months in the STC1-low group (HR = 0.83, 95% CI, 0.66–1.03; P = 0.087) and 4.41 versus 3.09 months in the STC1-high group (HR = 0.64, 95% CI, 0.49–0.84; P = 0.001). Altogether, high STC1 protein levels have a predictive potential to characterize a population of patients with chemorefractory mCRC and poor prognosis in whom regorafenib has an increased level of efficacy.
STC1 is a protein secreted by intratumor endothelial cells in which plasma concentrations increase in patients with chemorefractory mCRC. Based on analyses of patients with refractory mCRC in the TEXCAN and CORRECT trials, we found that STC1 plasma levels had a prognostic role for OS, with high levels associated with poor outcome. A predictive role for baseline STC1 levels was pointed out for regorafenib efficacy.
