The role of HER-3 expression in the prediction of clinical outcome for advanced colorectal cancer patients receiving irinotecan/cetuximab.

Abstract

404 Background: Preclinical data suggested that in presence of HER3 altered activation colorectal cancer cells may escape anti-EGFR mediated cell death. HER3 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 HER3 expression and clinical outcome in KRAS wild-type advanced colorectal cancer receiving cetuximab and irinotecan. Methods: We retrospectively analyzed immunoreactivity for HER3 in KRAS wild-type advanced colorectal cancer patients receiving irinotecan-cetuximab. Results: Eighty-four advanced KRAS wild- type colorectal cancer patients were available for HER3 analysis. Forty patients (48%) showed HER3 negative colorectal tumor, whereas the remaining 44 cases (52%) were deemed HER3 positive. In HER3 negative and HER3 positive tumors we observed a partial response in 17 (42%) and 8 (18%) patients respectively (p = 0.04). Progressive disease was obtained in 11 (35%) and 26 (53%) patients with respectively HER3 negative and positive tumor (p = 0.007). No differences were observed for stable disease. Median PFS was 6.3 months in patients showing HER3 negative tumors and 2.8 months for those who had HER3 overexpressing tumors (p < 0.0001). Median overall survival was 13.6 months in patients showing HER3 negative tumors and 10.5 months for those who had HER3-expressing tumors (p = 0.01). Conclusions: HER3 proved to be a predictive factor for clinical outcome in KRAS wild-type colorectal cancer patients treated with cetuximab. Combined HER3 and KRAS analysis may represent an effective strategy for a better selection of responding colorectal tumors. Furthermore besides identifying colorectal cancer patients refractory to EGFR directed treatment, HER3 overexpression may also represent a potential biological indicator for the development of a new class of antineoplastic agents in this setting. No significant financial relationships to disclose.