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Purpose: Although initially approved for metastatic colorectal cancer (mCRC) tumors with epidermal growth factor receptor (EGFR) overexpression, the use of anti-EGFR antibodies is now restricted to wild-type KRAS tumors. Little is known about prescribers' response to new clinical data, practice guidelines, and US Food and Drug Administration (FDA) label change with regard to the use of anti-EGFR antibodies in clinical practice. Methods: Commercially insured patients withmCRCwhoreceived second-line therapy between 2004 and 2010 were identified by dusing the LifeLink Health Plan Claims Database.We calculated the fraction of patients receiving anti-EGFR antibody in 2-month intervals. χ2 tests were used to compare treatment rates at four time points: time 1: June 2008, ASCO presentation of clinical data; time 2: February 2009, ASCO guidelines publication; time 3: August 2009, FDA label change; time 4: April 2010 to 8 months after FDA label change. Results: Five thousand eighty-nine patients received secondline therapy; of these, 2,599 patients received an anti-EGFR antibody. Median age was 60 years (range, 20 to 97), with 57% male sex. The majority of patients (59.4%) received an anti-EGFR antibody at time 1, with significant decrease at each of the subsequent time points (time 2: 46.2% [P=.019]; time 3: 35.2% [P<.001]; Time 4: 16.2% [P<.001]). Multivariable logistic regression did not show any affect of age, sex, comorbidities, or region of the country on this pattern. Conclusions: The use of anti-EGFR antibodies for mCRC decreased after the presentation of clinical trial data, ASCO guidelines publication, and FDA label change. These data suggest that oncologists respond rapidly to new evidence and professional guidelines, and readily incorporate predictive biomarkers into clinical practice. [ABSTRACT FROM AUTHOR]