Myc Gene Copy Number (gcn) and Sensitivity to Anti-Egfr Monoclonal Antibodies in Metastatic Colorectal Cancer (Mcrc)

e21018 Background: Monoclonal antibodies against Epidermal Growth Factor Receptor (EGFR) demonstrated efficacy in mCRC patients without mutations in the KRAS gene. Previous data in breast and lung cancer suggested that MYC GCN affects sensitivity to anti-EGFR agents. Methods: This retrospective study was conducted in a cohort of 303 mCRC patients treated with cetuximab/panitumumab, either alone (N=24) or in combination with chemotherapy (N=279). MYC GCN was assessed by fluorescence in situ hybridization (FISH) in primary colorectal cancer tissue samples. Results: In the study population response rate (RR) was 28%, median progression-free survival (PFS) 5.6 months and median overall survival (OS) 11.8 months. MYC was successfully evaluated in 298 cases and was amplified in 17 patients (5.7%). Individuals with MYC amplification showed a trend for a lower RR (7.7% versus 28.9%, p=0.12), shorter PFS (3.0 months versus 5.8 months, p=0.22) and shorter OS (11.3 months versus 12.6 months, p=0.15) than patients with non-amplified tumors. A Receiver Operating Characteristic (ROC) analysis was also performed in order to verify whether a better MYC GCN cut-off could discriminate between anti-EGFR sensitive and resistant cases. In this analysis, patients with mean MYC GCN ≥2.53 (N=199, 66.8%) had a significantly higher RR (32.2% versus 19.1%, p=0.02), a longer PFS (5.8 months versus 4.5 months, p=0.06) and a longer OS (12.3 months versus 11.4 months, p=0.59) than patients with mean GCN <2.53 (N=99, 33.2%). In order to assess the potential confounding effect of KRAS and BRAF status, we further analyzed the outcome of the 81 KRAS/BRAF wild-type patients according to MYC GCN. In this subset, a trend for improved RR (42% versus 20%, p=0.05), PFS (8.6 months versus 4.2 months, p=0.16) and OS (13.5 months versus 9.7 months, p=0.51) favored MYC FISH GCN ≥2.73 patients. Conclusions: MYC amplification is a rare event in mCRC, not significantly reducing sensitivity to anti-EGFR agents. A trend for better outcome was observed in presence of increased MYC GCN.