Two phase II randomized clinical trials comparing the addition of panitumumab vs. bevacizumab to standard cytotoxic therapy were presented at ASCO GI in January 2013. In the PEAK study, 285 patients with KRAS wild-type mCRC were treated with modified

FOLFOX6 with a PFS of 10.9 months for the group receiving panitumumab vs. 10.1 months for the group receiving bevacizumab (HR 0.87, P=0.35). Median OS had not been reached in the panitumumab group and was 25.4 months in the bevacizumab group (HR 0.72, P=0.14). Discontinuation rates were similar between the two arms (24% vs. 27%) and so Inhibitors,research,lifescience,medical were grade 3/4 adverse events (86% vs. 76%) (51). In the SPIRITT trial, 182 patients with KRAS wild-type mCRC previously treated with bevacizumab Inhibitors,research,lifescience,medical and an oxaliplatin-based regimen were randomized to FOLFIRI with panitumumab or bevacizumab as second line therapy. Median PFS [7.7 vs. 9.2 mo (HR 1.01)] and median OS [18.0 vs. 21.4 mo (HR 1.06)] were similar but response rates were higher in the panitumumab group (32% vs. 19%) (52).

CALGB 80405 is a randomized controlled trial which is comparing first-line cytotoxic chemotherapy with either cetuximab or bevacizumab (53). The results of this completed study will likely be available Inhibitors,research,lifescience,medical by the end of 2013. FIRE-3 is a randomized phase III trial comparing first-line FOLFIRI with either cetuximab or bevacizumab in mCRC and is expected to be reported Inhibitors,research,lifescience,medical at ASCO in 2013 (54). In our own institutional experience

with panitumumab the total number of previous chemotherapy regimens did not find protocol significantly affect median overall survival with panitumumab suggesting that the efficacy is retained across lines of therapy, a finding consistent with other Inhibitors,research,lifescience,medical studies (55). Liver limited disease The role of EGFR inhibitors in liver limited disease where the goal of therapy is to convert unresectable or borderline resectable tumors to resectable disease has been explored although to a limited Mephenoxalone extent. The phase II CELIM trial investigated cetuximab in combination with either an oxaliplatin- or irinotecan-based regimen in initially unresectable patients with isolated liver metastasis (defined as ≥5 tumors, technically unresectable on the basis of inadequate functional liver remnant, infiltration of both hepatic arteries/portal vein branches or infiltration of all hepatic veins). Objective responses were seen in 68% receiving FOLFOX with cetuximab and 57% in patients receiving FOLFIRI with cetuximab. R0 resection rates were high (38% and 30% in the two groups), but as no formal comparison was performed to a group without cetuximab, the benefit of adding an EGFR inhibitor in this setting is unclear (56).