e15063 Background: Accurate predictors of chemotherapy response and toxicity in CRC are required to improve the safety, efficacy and costs of treatment. Plasma proteomic profiling using multiple reaction monitoring mass spectrometry (MRM-MS) couples assay multiplexing with high specificity to determine levels of pre-selected biomarker proteins. Our aims were to investigate the utility of plasma proteomic profiling using MRM-MS for predicting: (1) early haematological toxicity, (2) response and (3) survival for patients receiving chemotherapy for CRC. Methods: Patients with locally advanced and metastatic CRC receiving chemotherapy were enrolled. Plasma collection was performed pre-chemotherapy, at day 3 and day 15 of treatment. Toxicity assessments (NCI Criteria v3.0) were prospectively collected for all patients and treatment response (RECIST) assessed for patients with metastatic disease. MRM-MS assays were designed for 39 peptides representing 31 liver derived plasma proteins with reported roles in inflammation and/or cancer. Statistical analysis was performed using the 2-sample t-test to assess statistically significant fold change differences (p<0.05) between sample days for: (1) patients with absence or presence of ≥ Grade 2 neutropenia after two cycles and (2) responders (CR and PR) versus non-responders (SD or PD). Results: Plasma proteomic profiling for 39 peptides was performed for 17 patients. The greatest change in protein levels was observed between Day 3 and 15 with 9% of proteins showing a 1.5 fold or greater change with some proteins showing a ≥ 200-fold change in level. Three proteins (clusterin, paraoxanse and apolipoprotein A1) were significantly different in the group analysed for neutropenia and four proteins (kininogen I, serum paraoxonase/ arylestease 1, apolipoprotein A-1 and complement C4a) were significantly different in the group analysed according to response. Survival analysis was not performed due to the short follow up. Discussion: Our results are encouraging for the use of a robust mass spectrometry technique for early prediction of neutropenia and chemotherapeutic response in CRC. No significant financial relationships to disclose.