Riccardo Giampieri et al., Prospective study of a molecular selection profile for RAS wild type colorectal cancer patients receiving irinotecan-cetuximab. Journal of Translational Medicine

Riccardo Giampieri1, Alessandra Mandolesi2, Khaled M Abouelkhair3, Cristian Loretelli1, Michela Del Prete1, Luca Faloppi1, Bianconi Maristella1, Ezzeldin M Ibrahim3, Marina Scarpelli2, Stefano Cascinu1 and Mario Scartozzi4

1Department of Medical Oncology, University Hospital of Ancona, Polytechnic University of the Marche
2Department of Pathology, University Hospital of Ancona, Polytechnic University of the Marche
3Department of Medical Oncology, International Medical Center of Jeddah
4Department of Medical Oncology, Medical Oncology, University Hospital of Cagliari, University of Cagliari


The 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.

K-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).

Forty-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).

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


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