Blood‐based markers of efficacy and resistance to cetuximab treatment in metastatic colorectal cancer: results from CALGB 80203 (Alliance)

摘要: Circulating protein markers were assessed in patients with colorectal cancer (CRC) treated cetuximab CALGB 80203 to identify prognostic and predictive biomarkers. Patients locally advanced or metastatic CRC received FOLFOX FOLFIRI chemotherapy (chemo) chemo combination cetuximab. Baseline plasma samples from 152 analyzed for six candidate [epidermal growth factor (EGF), heparin-binding EGF (HBEGF), epidermal receptor (EGFR), HER2, HER3, CD73]. Analyte levels associated survival endpoints using univariate Cox proportional hazards models. Predictive identified a treatment-by-marker interaction term the model. Plasma of EGF, HBEGF, CD73 overall (OS) across all (KRAS mutant wild-type). High predicted lack OS benefit KRAS wild-type (WT) (chemo HR = 0.98, 95% CI 0.74-1.29; chemo+cetuximab 1.54, 1.05-2.25; P 0.045) 1.72, 1.02-2.92; 0.90, 0.67-1.21; 0.026). Across patients, higher HER3 significant treatment 4.82, 1.68-13.84; 0.95, 0.31-2.95; 0.046). was also as WT 1.28, 0.88-1.84; 0.60, 0.32-1.13; 0.049). Although these results are preliminary, confirmatory studies necessary before clinical application, data suggest that may play important roles biological response