SO-20 Stanniocalcin 1 (STC1) in patients with refractory colorectal cancer (CRC) treated with regorafenib: An exploratory analysis of the CORRECT trial

We previously described a prognostic role for the glycoprotein STC1 in patients with metastatic CRC (mCRC) receiving first-line chemotherapy and in a small number of patients with refractory mCRC previously treated with regorafenib (Jary, et al. Int J Cancer 2020). Regorafenib is approved for the treatment of patients with mCRC based an improvement in overall survival (OS) in the placebo-controlled, randomized, phase 3 CORRECT trial (Grothey, et al. Lancet 2013; NCT01103323). Here, we investigate the relationship between STC1 and clinical outcome in patients from CORRECT. In this exploratory analysis, STC1 protein levels were measured by ELISA in plasma samples collected at baseline. The relationship between STC1 levels and OS was evaluated using a Cox proportional hazards model. Of 679 patients with available plasma samples, STC1 levels were evaluable in 646 patients (placebo n=211; regorafenib n=435). The baseline characteristics of the biomarker cohort were similar to the overall cohort. The overall median STC1 value was 1203 pg/mL (range: 320–6568). STC1 levels were comparable between the regorafenib (median: 1181 pg/mL; range: 375–6568) and placebo (median: 1232 pg/mL; range: 320–6223) cohorts. The cutoff for the prognostic effect was optimized based on a Cox model for OS combining both regorafenib and placebo arms. Patients with STC1 levels at 1437 pg/mL or higher (n=246) had a median OS of 3.81 months (95% CI 3.45–4.47) versus 7.63 months (95% CI 7.04–8.45) for patients with levels below 1437 pg/mL (n=400). The prognostic value of STC1 levels at baseline was significant in patients included in both the placebo group (HR 2.69, 95% CI 1.99–3.63; p < 0.001) and in the regorafenib group (HR 1.90, 95% CI 1.55–2.32; p < 0.001). We next assessed if STC1 levels could predict regorafenib efficacy. The optimized cutoff for the prognostic effect was used to assess the predictive effect of regorafenib versus placebo on OS. In the presence of high levels of STC1, OS was improved with regorafenib (median OS: 4.41 months, 95% CI 3.75–5.19) versus placebo (median OS: 3.09 months, 95% CI 2.56–3.91; p=0.001). The interaction p-value between STC1 levels and treatment for OS was 0.044 (STC1 high: HR 0.64, 95% CI 0.49–0.84; STC1 low: HR 0.83, 95% CI 0.66–1.03). We identified STC1 as a prognostic marker in patients with refractory mCRC. High STC1 protein levels characterized a population of patients with poor prognosis who benefit most from treatment with regorafenib.