Background: Metastatic colon cancer (mCC) patients may receive multiple lines of treatment (Tx1, Tx2, etc.) consisting of one or more cytotoxic (CYT: 5FU/LV, oxaliplatin [OX], irinotecan [IRI]) and biologic (BIO: bevacizumab [BEV], cetuximab [CET], panitumumab [PAN]) drugs. The National Comprehensive Cancer Network (NCCN) provides evidence-based Tx recommendations for each line. The objective of this study was to examine real-world clinical practice patterns between 2002 and 2010. In particular, we compared the most common regimens across Tx lines and how Tx patterns changed over time. We also documented the uptake and use of new BIOs. Methods: We used population-based SEER-Medicare data to determine Tx1, Tx2, and Tx3 regimens of 4,616 mCC patients (the median age at diagnosis was 78) diagnosed in 2003-2009 and followed through 2010. We will use an algorithm previously developed by us to identify regimens. Results: The most common CYT backbone in Tx1 was OX (51% of patients) followed by 5FU/LV (30%). In comparison, IRI was a preferred choice in Tx2 (65%) and Tx3 (31%). In 2003, the most common Tx1 regimens were 5FU/LV- (56%) and IRI-based (35%). 5FU/LV and IRI use decreased to 22% and 9% respectively in 2009, while OX use increased from 7% in 2003 to 63% in 2009. In 2004, the FDA approved BEV for Tx1. BEV’s share increased from 9% in 2004 to 53% in 2005. BEV was used in 9% of Tx2 regimens in 2004 and 46% in 2005. CET was approved in 2004. CET was used in less than 5% of Tx1 regimens in any year up to 2010. CET use in Tx2 increased from 19% to 27% between 2005 and 2007, and declined to 23% in 2010. The FDA approved PAN in September 2006 for treatment after failure of CYT-based regimens, i.e., primarily in Tx3 and beyond. Only 350 (8%) of patients received Tx3, and of these 59 (17%) received PAN without a CYT backbone. One in three Tx3 regimens consisted of biologics only (54% CET, 43% PAN). Conclusions: This study used SEER-Medicare registry data to examine and document real-world clinical practice patterns in treatment of elderly mCC patients between 2003 and 2010. We observed that as new biologic agents were introduced to the market, variations in the combinations and the number of treatment have significantly and rapidly changed.