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. 2011;16(1):53-60.
doi: 10.1634/theoncologist.2010-0119. Epub 2011 Jan 6.

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

Mario Scartozzi  1 , Alessandra Mandolesi, Riccardo Giampieri, Alessandro Bittoni, Chiara Pierantoni, Alberto Zaniboni, Eva Galizia, Lucio Giustini, Rosa Rita Silva, Renato Bisonni, Rossana Berardi, Tommasina Biscotti, Simona Biagetti, Italo Bearzi, Stefano Cascinu
Affiliations

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

Mario Scartozzi et al. Oncologist. 2011.

Abstract

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.

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Conflict of interest statement

Disclosures

Mario Scartozzi: None; Alessandra Mandolesi: None; Riccardo Giampieri: None; Alessandro Bittoni: None; Chiara Pierantoni: None; Alberto Zaniboni: None; Eva Galizia: None; Lucio Giustini: None; Rosa Rita Silva: None; Renato Bisonni: None; Rossana Berardi: None; Tommasina Biscotti: None; Simona Biagetti: None; Italo Bearzi: None; Stefano Cascinu: None.

Section Editor Richard Goldberg discloses a consulting relationship with Amgen, AstraZeneca, Bayer, Bristol-Myers Squibb, Genentech, Genomic Health, Lilly, and sanofi-aventis; and research funding from Amgen, Bayer, Genentech, sanofi-aventis, and Enzon.

Section Editor Patrick Johnston discloses employment with Almac Diagnostics; intellectual property including 12 patients; a consulting relationship with Almac, Roche, Chugai Pharmaceuticals, and sanofi-aventis; honoraria received from AstraZeneca, Chugai Pharmaceuticals, Pfizer, sanofi-aventis, Roche, and ASCO; research funding from AstraZeneca and Amgen; and ownership interests in Almac Diagnostics and Fusion Antibodies.

Section Editor Peter O'Dwyer discloses a consulting relationship with Tetralogic Pharmaceuticals, PrECOG, and AstraZeneca; an advisory relationship with Nereus Pharmaceutical, Tetralogic Pharmaceuticals, and PrECOG; research support from Pfizer, Bristol-Myers Squibb, Methylgene, Novartis, Genentech, Bayer, Merck, Kosan, Ardea, and Exelixis; honoraria received from Genentech, Bayer, Methylgene, and Bristol-Myers Squibb; and ownership interest with Tetralogic Pharmaceuticals.

Reviewer “A” discloses no financial relationships.

Reviewer “B” discloses no financial relationships.

The content of this article has been reviewed by independent peer reviewers to ensure that it is balanced, objective, and free from commercial bias. On the basis of disclosed information, all conflicts of interest have been resolved.

Figures

Figure 1.
Figure 1.
Receiver operating characteristic analysis based on human epidermal growth factor receptor 3 expression results with response to cetuximab therapy as the endpoint. In this model, the sensitivity was 92% (95% confidence interval [CI], 74%–99%) and specificity was 96.7% (95% CI, 88.5%–99.6%). The area under the curve was 0.95 (p = .0001).
Figure 2.
Figure 2.
Kaplan–Meier curves for the median progression-free survival intervals of colorectal cancer patients treated with irinotecan and cetuximab showing human epidermal growth factor receptor (HER)-3 tumor overexpression (dotted line) and without HER-3 tumor overexpression (solid line)—2.8 versus 6.3 months, respectively (p < .0001).
Figure 3.
Figure 3.
Kaplan–Meier curves for the median overall survival duration of colorectal cancer patients treated with irinotecan and cetuximab showing tumor human epidermal growth factor receptor (HER)-3 overexpression (dotted line) and without tumor HER-3 overexpression (solid line)—10.5 months versus 13.6 months, respectively (p = .01).
See this image and copyright information in PMC

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