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miR128 and LET-7 microRNAs as potential biomarkers for selection of patients with metastatic colorectal cancer candidate to cetuximab/panitumumab therapy.

3636 Background: Monoclonal antibodies against epidermal growth factor receptor (EGFR) such as cetuximab and panitumumab demonstrated efficacy in metastatic colorectal cancer patients (mCRC) without mutations in the KRAS gene. MicroRNAs are a new class of non coding RNAs implicated in cancer biology, with miR128 and Let-7 family implicated respectively, in EGFR and KRAS regulation activity. Aim of the present study was to define whether miR128 and Let-7 levels affected response to cetuximab or panitumumab in mCRC.


METHODS
The study was conducted in a cohort of 89 mCRC treated with cetuximab/panitumumab either alone (N=7) or in combination with chemotherapy (N=82). Patients were analyzed for Let-7 and miR128 levels using Agilent's miRNA platform.


RESULTS
Among the 89 patients included onto the study, miR128 and Let-7 levels were successfully performed in 78 cases. In the study population response rate (RR) was 21.8%, median progression free survival (PFS) 4.3 months and median survival (OS) 12.6 months. Compared to patients with high miR128 (N=43), individuals with low miR128 levels (N=35) had significantly lower RR (8.5% vs 32.5%, p= 0.05) , PFS (2.6 vs 5.2 months, HR= 0.42; p=0.02) and OS (8.1 vs 16.4 months, HR=0.36; p=0.02). High levels of Let-7 (N=40) associated with significantly longer PFS (5.6 vs 2.2 months, HR= 0.52; p=0.002) and OS (16.4 vs 8.4 months, HR= 0.47; p=0.03). In the group of patients with KRAS mutation ( N=32) low levels of miR128 were significantly associated with shorter PFS (1.8 vs 4.5 months, HR=0; p=0.02) and OS (5.8 vs 16.2 months, HR=0.36; p=0.04), while high Let-7 levels associated with longer PFS (3.3 vs 2.1 months, HR=0.33; p=0.11) and OS (16.2 vs 5.8 months, HR=0.36; p=0.04). In the KRAS wild type population (N=38) high Let-7 levels identified patients with higher probability to respond (odds ratio= 2.44), with the lowest risk of progression (HR=0.87) and death (HR=0.75).


CONCLUSIONS
Our results suggest that miR128 and Let-7 are biomarkers potentially useful for selection of mCRC potentially candidate for anti-EGFR agents. A confirmatory study is ongoing. We thank AIRC Associazione Italiana Ricerca contro il Cancro for supporting the study.