The Role of HER-3 Expression in the Prediction of Clinical Outcome for Advanced Colorectal Cancer Patients Receiving Irinotecan and Cetuximab

Abstract

Learning Objectives: After completing this course, the reader will be able to: Describe the relationship between HER-3 status and response to treatment with cetuximab and irinotecan in patients with advanced colorectal cancer and EGFR+ wild-type K-RAS mutation in this study.Evaluate data that support using HER-3 status as a predictive factor for anti-EGFR treatment response in patients with colorectal cancer. CME This article is available for continuing medical education credit at CME.TheOncologist.com Preclinical data suggested that, in the presence of human epidermal growth factor receptor (HER)-3–altered activation, colorectal cancer cells may escape anti–epidermal growth factor receptor (EGFR)-mediated cell death. HER-3 overexpression may then represent a key factor for resistance to anti-EGFR antibodies in colorectal cancer. The aim of our analysis was to investigate a possible correlation between HER-3 expression and clinical outcome in wild-type K-RAS advanced colorectal cancer patients receiving cetuximab and irinotecan. We retrospectively analyzed immunoreactivity for HER-3 in wild-type K-RAS advanced colorectal cancer patients receiving irinotecan and cetuximab. Eighty-four advanced wild-type K-RAS colorectal cancer patients were available for HER-3 analysis. Forty patients (48%) had a HER-3− colorectal tumor, whereas the remaining 44 cases (52%) were deemed HER-3+. In patients with HER-3− and HER-3+ tumors, we observed a partial response in 17 (42%) and eight (18%) patients respectively; progressive disease occurred in 11 (35%) and 26 (53%) patients with HER-3− and HER-3+ tumors, respectively (p = .003). The median progression-free survival time was 6.3 months in patients with HER-3− tumors and 2.8 months for those who had HER-3–overexpressing tumors (p < .0001). The median overall survival time was 13.6 months in patients showing HER-3− tumors and 10.5 months for those who had HER-3–expressing tumors (p = .01). HER-3 proved to be a predictive factor for clinical outcome in wild-type K-RAS colorectal cancer patients treated with cetuximab. Combined HER-3 and K-RAS analysis may represent an effective strategy for better selection of responding colorectal cancer patients.