Background: 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. Methods: 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). Results: 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). Conclusions: Our results suggest that prospective selection of optimal candidates for cetuximab treatment is feasible and may be able to improve clinical outcome.
Prospective study of a molecular selection profile for RAS wild type colorectal cancer patients receiving irinotecan-cetuximab / R. Giampieri, A. Mandolesi, K. M Abouelkhair, C. Loretelli, M. Del Prete, L. Faloppi, M. Bianconi, E. M Ibrahim, M. Scarpelli, S. Cascinu, M. Scartozzi. - In: JOURNAL OF TRANSLATIONAL MEDICINE. - ISSN 1479-5876. - 13:1(2015 May 07), p. 140.140.
|Titolo:||Prospective study of a molecular selection profile for RAS wild type colorectal cancer patients receiving irinotecan-cetuximab|
|Parole Chiave:||Anti-EGFR; BRAF; Cetuximab; Colorectal cancer; HER-3; IGF-1; PIK3CA; Prospective selection; RAS; adult; aged; aged, 80 and over; antineoplastic combined chemotherapy protocols; biomarkers, tumor; Camptothecin; Cetuximab; Class I phosphatidylinositol 3-kinases; colorectal neoplasms; dna mutational analysis; disease-free survival; exons; female; gtp phosphohydrolases; humans; in situ hybridization, fluorescence; insulin-like growth factor i; male; membrane proteins; middle aged; phosphatidylinositol 3-kinases; prospective studies; proto-oncogene proteins p21(ras); receptor, epidermal growth factor; receptor, erbb-3; treatment outcome; biochemistry, genetics and molecular biology (all)|
|Settore Scientifico Disciplinare:||Settore MED/06 - Oncologia Medica|
Settore BIO/12 - Biochimica Clinica e Biologia Molecolare Clinica
Settore BIO/13 - Biologia Applicata
Settore MED/04 - Patologia Generale
Settore MED/03 - Genetica Medica
|Data di pubblicazione:||7-mag-2015|
|Digital Object Identifier (DOI):||http://dx.doi.org/10.1186/s12967-015-0501-5|
|Appare nelle tipologie:||01 - Articolo su periodico|
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