title: The role of HER-3 expression in the prediction of clinical outcome for advanced colorectal cancer patients receiving irinotecan and cetuximab.
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.
authors.affiliation: Clinica di Oncologia Medica, AO Ospedali Riuniti, Università Politecnica delle Marche, Via Conca, 60020, Ancona, Italy.
authors.forename: Mario
authors.initials: M
authors.lastname: Scartozzi
authors.forename: Alessandra
authors.initials: A
authors.lastname: Mandolesi
authors.forename: Riccardo
authors.initials: R
authors.lastname: Giampieri
authors.forename: Alessandro
authors.initials: A
authors.lastname: Bittoni
authors.forename: Chiara
authors.initials: C
authors.lastname: Pierantoni
authors.forename: Alberto
authors.initials: A
authors.lastname: Zaniboni
authors.forename: Eva
authors.initials: E
authors.lastname: Galizia
authors.forename: Lucio
authors.initials: L
authors.lastname: Giustini
authors.forename: Rosa Rita
authors.initials: RR
authors.lastname: Silva
authors.forename: Renato
authors.initials: R
authors.lastname: Bisonni
authors.forename: Rossana
authors.initials: R
authors.lastname: Berardi
authors.forename: Tommasina
authors.initials: T
authors.lastname: Biscotti
authors.forename: Simona
authors.initials: S
authors.lastname: Biagetti
authors.forename: Italo
authors.initials: I
authors.lastname: Bearzi
authors.forename: Stefano
authors.initials: S
authors.lastname: Cascinu
mesh_terms: D000328:Adult; D000368:Aged; D000369:Aged, 80 and over; D000911:Antibodies, Monoclonal / Q000008:administration & dosage; D061067:Antibodies, Monoclonal, Humanized; D000971:Antineoplastic Combined Chemotherapy Protocols / Q000627:therapeutic use*; D002166:Camptothecin / Q000008:administration & dosage / Q000031:analogs & derivatives; D000068818:Cetuximab; D015179:Colorectal Neoplasms / Q000188:drug therapy* / Q000201:enzymology* / Q000235:genetics / Q000473:pathology; D018572:Disease-Free Survival; D005260:Female; D011905:Genes, ras; D006801:Humans; D007150:Immunohistochemistry; D000077146:Irinotecan; D008297:Male; D008875:Middle Aged; D009154:Mutation; D011379:Prognosis; D020893:Receptor, ErbB-3 / Q000096:biosynthesis* / Q000235:genetics; D012189:Retrospective Studies; D016896:Treatment Outcome
chemical_list: D000911:Antibodies, Monoclonal; D061067:Antibodies, Monoclonal, Humanized; D000077146:Irinotecan; D020893:Receptor, ErbB-3; D000068818:Cetuximab; D002166:Camptothecin