Management of folinic acid administration in patients with metastatic colo-rectal cancer

Abstract

therapy. However, an in-deep molecular selection might overcome the predictive role of primary tumour location in this setting. Patients and methods: We conducted a retrospective analysis in which tumour samples from RAS/BRAF wild type (WT) metastatic CRC patients treated with secondthird-line irinotecan/cetuximab were analysed for EGFR Gene Copy Number (GCN) and promoter methylation. Study objective was to evaluate the correlation of tumour sidedness, EGFR promoter methylation and EGFR GCN with clinical outcome. Median follow up duration was 14.3 months. Results: Eighty-eight patients were included in the study, 27.3% had right sided CRC, 72.7% had left sided CRC; 36.4% had EGFR GCN<2.12 tumour, 63.6% had EGFR GCN2.12 tumour; 50% had EGFR promoter methylated tumour. Right Sided Colorectal Cancer (RSCRC) were associated with reduced Overall Response Rate (ORR) (4.2% for RSCRC vs. 35.9% for Left Sided Colorectal Cancer (LSCRC), p ¼ 0.0030), shorter Progression free Survival (PFS) (3.0 vs. 6.75 months, p < 0.0001) and shorter Overall Survival (OS) (8 vs. 13.6 months, p < 0.0001). EGFR GCN < 2.12 tumours were associated with reduced ORR (6.2% for EGFR GCN < 2.12 vs 39.3% for EGFR GCN 2.12 tumours, p ¼ 0.0009), shorter PFS (3.5 vs. 6.5 months, p ¼ 0.0006) and shorter OS (8.5 vs. 14.0 months, p < 0.0001). EGFR methylated tumours were associated with reduced ORR (9.1% for methylated vs. 45.5% for unmethylated, p ¼ 0.0001), shorter PFS (3 vs. 7.67 months, p < 0.0001) and shorter OS (8 vs. 17 months, p < 0.0001). At multivariate analysis EGFR GCN and EGFR promoter methylation maintained their independent role for ORR (respectively p ¼ 0.0082 and 0.0025), PFS (respectively p ¼ 0.0048 and < 0.0001) and OS (respectively p ¼ 0.0001 and < 0.0001). Conclusions: In our study an accurate molecular selection based on an all RAS and BRAF analysis along with EGFR GCN and EGFR promoter methylation status seems to be more relevant than primary tumour sidedness in the prediction of clinical outcome during cetuximab/irinotecan therapy. However, these data need to be validated with future prospective and translational studies.