Molecular And Clinical Analysis Of Predictive Biomarkers To Anti-Egfr Inhibitors In Metastatic Colorectal Cancer (Mcrc): Interaction Among Early Tumor Shrinkage, Skin Toxicities, And Ras Status.

e14680 Background: Since the introduction in clinical practice of anti-EGFR therapies different studies were focused on the identification of clinical and molecular predictive biomarkers. The purpose of our study is to investigate the predictive value of early tumor-shrinkage (ETS) and skin toxicity (ST) in correlation with KRAS and NRAS status in pts affected by mCRC treated with Cetuximab-regimens (C). Methods: In this observational retrospective study we included a total of 29 mCRC consecutive patients (pts) (18M/11F) RAS status wild type (WT) chemonaïve. Mutant alleles of KRAS exon 3 (codons 59 and 61) and exon 4 (codons 117 and 146) and NRAS exon 2 (codons 12 and 13), exon 3 (codons 59 and 61) and exon 4 (codons 117 and 146) were detected. Clinical data were recorded. ETS was defined as a change of ≥ 20% in the sum of the longest diameters of target lesions compared to baseline. We used for ST is the National Cancer Institute Common Terminology Criteria for Adverse Events version 4.0 (NCI CTCAE v4.0). The correlation between RAS status and outcomes was investigated by Yates' chi-square. Survival analysis was performed by Kaplan-Meier method using RAS status and ETS as strata variable. P-values < 0.05 were considered statistically significant. Results: The median follow-up time was 34.2 months (range 6 – 81). ETS was recorded in 10 pts (52.6%) and was significantly associated with RAS status (p = 0.028). Moreover, RAS status (p = 0.003) and ETS (p = 0.006) were significantly associated with longer OS. Grade 2-3 ST was reported in 15 pts and correlate significantly with OS (p = 0.024). Conclusions: Selecting pts who will benefit most from treatment with anti-EGFR agents is an important goal. ETS represents a new valid clinical biomarker to determine which pts are more likely to receive survival benefit from Cetuximab. Further studies are warranted in order to personalize cancer therapy obtaining best results with less toxicities.