Revised text to state that a meta-analysis of the randomized studies, which were all done in the era when only fluoropyrimidines were available for systemic therapy, did not demonstrate a survival advantage (cited Mocellin et al. as reference 40).
Added text to include aflibercept as one of the eight active and approved drugs for patients with metastatic colorectal cancer.
Added text to state that a major question was whether the use of bevacizumab after first-line therapy was warranted when bevacizumab was used as a component of first-line therapy; added that at the 2012 American Society of Clinical Oncology Annual Meeting data was presented from a randomized, controlled trial of patients with metastatic colorectal cancer who were randomly assigned to chemotherapy without bevacizumab or chemotherapy with bevacizumab (cited Arnold et al. as reference 62 and level of evidence 1iiA).
Added Aflibercept as a new subsection.
Added text to state that because cetuximab affects tyrosine kinase signaling at the surface of the cell membrane, tumors with mutations causing activation of the pathway downstream of the EGFR are not sensitive to its effects; the addition of cetuximab to multiagent chemotherapy improves survival in patients with colon cancers that lack a KRAS mutation.
Added text to state that the OPUS study sought to evaluate the effect of adding cetuximab to first-line treatment with a FOLFOX regimen in an open-labeled, randomized, multicenter, phase II study of patients with EGFR-expressing metastatic colorectal cancer (cited Bokemeyer et al. as reference 69 and level of evidence 1iiD).
Added text to state that in clinical trials, panitumumab demonstrated efficacy as a single agent or in combination therapy, which was consistent with the effects on PFS and overall survival with cetuximab; there appears to be a consistent class effect.