Prospective study of a molecular selection profile for RAS wild type colorectal cancer patients receiving irinotecan-cetuximab

• DOI: 10.1186/s12967-015-0501-5
• Publication Date: 2015-05-05T22:45:56Z
• Authors: Riccardo Giampieri; Alessandra Mandolesi; Khaled M Abouelkhair; Cristian Loretelli; Michela Del Prete; Luca Faloppi; Bianconi Maristella; Ezzeldin M Ibrahim; Marina Scarpelli; Stefano Cascinu; Mario Scartozzi
• Keywords: Adult; Male; Receptor, ErbB-3; Class I Phosphatidylinositol 3-Kinases; DNA Mutational Analysis; Cetuximab; Prospective selection; Irinotecan; Disease-Free Survival; BRAF; GTP Phosphohydrolases; Proto-Oncogene Proteins p21(ras); Phosphatidylinositol 3-Kinases; 03 medical and health sciences; 0302 clinical medicine; Antineoplastic Combined Chemotherapy Protocols; Biomarkers, Tumor; Humans; Prospective Studies; Insulin-Like Growth Factor I; In Situ Hybridization, Fluorescence; Anti-EGFR; Aged; 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); Medicine(all); Aged, 80 and over; Biochemistry, Genetics and Molecular Biology(all); Research; Membrane Proteins; PIK3CA; Exons; Middle Aged; Colorectal cancer; 3. Good health; ErbB Receptors; Treatment Outcome; HER-3; IGF-1; Camptothecin; Female; Colorectal Neoplasms; RAS

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.