606P - Body Mass Index and Impaired Fasting Blood Glucose as Predictive Factors of Efficacy in Cetuximab-Based Colorectal Cancer Treatment

Abstract

ABSTRACT Introduction Cetuximab is an anti-EGFR monoclonal antibody with antitumor efficacy in metastatic colorectal cancer harboring wild-type K-Ras gene. However, not all patients K-Ras wild-type benefit from Cetuximab, underscoring the need for additional markers to help in patient selection. Preclinical evidences suggest that the EGFR and Insulin-like Growth Factor-1 Receptor (IGF-1R) pathways interact to drive tumor growth and survival. It's well known that in hyperinsulinemic state, higher insulin levels upregulate IGF-1 production, leading this state a potential biomarker for Cetuximab efficacy. The aim of our study was to evaluate the feasibility to stratify patients more likely to benefit from Cetuximab treatment using two well known signs of hyperinsulinemic state such as the high Body Mass Index (BMI) and impaired Fasting Blood Glucose (FBG). Methods We retrospectively collected 250 K-Ras wild-type metastatic colorectal cancer patients treated with Cetuximab containing regimens in first to fifth line setting. From this cohort we selected 76 patients treated with Cetuximab + CPT11 after failure of first line CPT11 based containing regimen. We divided this population into two groups according to the presence of both elevated BMI (cut-off 24.99 sec. WHO Criteria) and high FBG (cut-off 100 mg/dL sec American Diabetes Association) and we evaluated the Time To Progression (TTP) of these two groups. Results We found a statistically significant lower TTP in patients with both elevated BMI and FBG compared to patients with presence of none or only one of the two parameters (median TTP 4.3 months, CI95%:2.5-5.4 vs 5.6 months, CI95%:2.5-5.8; P = 0.034). Conclusions The statistically significant poorer outcome in patients with both BMI and FBG treated with Cetuximab + CPT11 after CPT11 failure could be explained by the reduction of Cetuximab efficacy due to the probable presence of upregulation of vicar pathways such as IGF-1R linked to hyperinsulinemic state. If confirmed in larger populations and in perspective studies the hyperinsulinemic state may represent a new predictive marker of efficacy in this type of population. Disclosure All authors have declared no conflicts of interest.