OBJECTIVES: Study examined the pattern of chemotherapy and biologic therapy use by line of treatment in newly diagnosed patients with colorectal cancer (CRC). METHODS: Patients newly diagnosed with CRC between January 1, 2005 and June 31, 2009 and treated with systemic therapy were identified in a US-based administrative medical claims (i3 Innovus) database.  Six months of patient history with no prior ICD-9 diagnosis of CRC and 1-year post-index continuous enrollment was required. Patients were followed from initial CRC diagnosis to death, disenrollment, or June 31, 2010. Chemotherapy and biologic treatments over time were analyzed to identify lines of therapy and assessed and stratified by line of therapy (1st, 2nd, 3rd +), subgroup analysis was performed in metastatic CRC. RESULTS: Of 9876 patients, 45% received only 1st line treatment, 35% received 1st and 2nd line treatment and 20% received 3rd line and beyond. 60% of the study patients were identified as having metastasis either during the follow up period or at index date. The 1st line, 43% received an oxaliplatin-based regimen, 5% received an irinotecan-based regimen, and 46% received 5-FU alone.  2nd and 3rd line settings percentages of patients treated with irinotecan-based regimens increased from 18% to 43%, respectively, use of oxaliplatin-based regimens dropped from 42% to 22%, respectively. The proportion of subjects who used bevacizumab doubled from 1st to 3rd line regimen. Overall, use of cetuximab and panitumumab increased from 2% in the 1st line to 7%, and 23%, respectively in the 2nd and 3rd + lines of treatment. CONCLUSIONS: Despite treatment guidelines, a large proportion of patients received 5-FU monotherapy and capecitabine  as 1st line treatment even for metasteses. The use of biologics in the first line was present with use in later lines.  The use of EGFR inhibitors increased in the later lines of treatment after FOLFOX and FOLFIRI with or without bevacizumab.