Searching for Circulating Proteins As New Biomarkers/potential Therapeutic Targets in Advanced Pancreatic Cancer Patients.

e16219 Background: Ca19.9 is the only validated biomarker in pancreatic cancer. Novel biomarkers are needed. Methods: Plasma samples from ECOG 0-1 metastatic pancreatic cancer patients (n = 20) were colected prospectively before (basal time, Bt) and after one cycle (1Ct) of first-line nab-paclitaxel plus gemcitabine therapy (AG). A 440 protein multiplex ELISA array was run in the 40 plasma samples. The cohort was followed up for a median of 12 months (m) for progression free survival (PFS), overall survival (OS) and overall response rate (ORR). Survival curves estimated using Kaplan-Meier were compared with log-rank tests. Results: Median PFS 9,2m (95% CI 3.2-14.5) and OS 13.5m (95% CI 4.4-20.5); ORR: CR/PR/SD/PD 0/8/11/1. At Bt: Proteins predictive for both PFS and OS: IL18Rb, CCL13 (MCP), Decorin, Pepsinogen and CXCL5 (ENA78); Proteins predictive for ORR: FcgRIIBC, IL15R, Lipocalin2, ESAM, Activin A, WIF1, Galectin 1 and TECK; Proteins predictive only for PFS: IL17F, CCL17, Adipsin, CRP, MMP2, Chemerin, Thrombomodulin, Transferrin, CA9, Eotaxin, IL5 ans IL10; Proteins predictive only for OS: NRG1b1, ICAM2 (CD102), DLK1, Lox1, CXCL14, CHI3L1, P-cadherin, IL32a and FGF7. At 1Ct: only IL18Rb was predictive for both PFS and OS; only FcgRIIBC and IL15R were predictive for ORR. Conclusions: Higher plasma levels of IL18Rb are strong predictors of better survival. Higher plasma levels of FcgRIIBC and/or lower plasma levels of IL15R are key factors of response to AG. These proteins deserve further evaluation both as biomarkers and as potential therapeutic targets. IL18Rb plasma levels OS Bt (m) p = 0.049 OS 1Ct (m) p = 0.021 PFS Bt (m) p = 0.004 PFS 1Ct (m) p < 0.001 < Median 9.8 (7.08-11.8) 9.0 (5.58-12.4) 7.1 (4.46-9.73) 5.8 (4.46-9.73) > Median 17.8 (10.4-25,06) 17.8 (10.4-25,06) 11.8 (9.3-14.3) 13.1 (9.3-14.3 PD (n = 8) SD p-value Test X SD X SD FcgRIIBC Bt 1610.69 848.21 736.02 541.11 0.014 Student t FcgRIIBC 1Ct 254.07 404.16 -155.53 466,32 0.041 UMannW IL15R Bt 1.63 4.60 16.87 21.25 0.030 UMannW IL15R 1Ct -1,28 3.62 13.78 21.28 0.031 UMannW