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Journal of Translational Medicine

, 13:140

First Online: 07 May 2015Received: 23 February 2015Accepted: 22 April 2015DOI: 10.1186-s12967-015-0501-5

Cite this article as: Giampieri, R., Mandolesi, A., Abouelkhair, K.M. et al. J Transl Med 2015 13: 140. doi:10.1186-s12967-015-0501-5

Abstract

BackgroundThe aim of our study was to evaluate whether a panel of biomarkers, prospectively analysed might be able to predict patients’ clinical outcome more accurately than RAS status alone.

MethodsK-RAS exons 2, 3, 4 wild type colorectal cancer patients, candidates to second-third-line cetuximab with chemotherapy were prospectively allocated into 2 groups on the basis of their profile: favourable BRAF and PIK3CA exon 20 wild type, EGFR GCN ≥ 2.6, HER-3 Rajkumar score ≤ 8, IGF-1 immunostaining < 2 or unfavourable any of the previous markers altered or mutated. After the introduction of N-RAS status exons 2, 3, 4 only RAS wild type patients were considered eligible.

Primary aim was response rate RR. To detect a difference in terms of RR among patients with an unfavourable profile estimated around 25% and patients with a favourable profile estimated around 60%, with a probability alpha of 0.05 and beta of 0.05, required sample size was 46 patients. Secondary endpoints were progression free survival PFS and overall survival OS.

ResultsForty-six patients were enrolled. Seventeen patients 37% were allocated to the favourable and 29 patients 63% to the unfavourable profile. RR in the favourable and unfavourable group was 11-17 65% and 2-29 7% p = 0.007 respectively. The favourable group also showed an improved PFS 8 months vs. 3 months, p < 0.0001 and OS 15 months vs. 6 months, p < 0.0001.

ConclusionsOur results suggest that prospective selection of optimal candidates for cetuximab treatment is feasible and may be able to improve clinical outcome.

KeywordsProspective selection Anti-EGFR Cetuximab Colorectal cancer RAS BRAF HER-3 IGF-1 PIK3CA  Download fulltext PDF



Autor: Riccardo Giampieri - Alessandra Mandolesi - Khaled M Abouelkhair - Cristian Loretelli - Michela Del Prete - Luca Faloppi -

Fuente: https://link.springer.com/







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