Rectal Cancer Treatment (PDQ®): Treatment - Health Professional Information [NCI] - Stage IV and Recurrent Rectal Cancer
Cetuximab is a partially humanized monoclonal antibody against the epidermal growth factor receptor (EGFR). For patients who have progressed on irinotecan-containing regimens, a randomized phase II study was performed of either cetuximab or irinotecan and cetuximab. The median TTP for patients receiving cetuximab was 1.5 months compared to median TTP of 4.2 months for patients receiving irinotecan and cetuximab.[Level of evidence: 3iiiDiv] On the basis of this study, cetuximab was approved for use in patients with metastatic colorectal cancer refractory to 5-FU and irinotecan.
The Crystal Study (EMR 62202-013 [NCT00154102]) randomly assigned 1,198 patients with stage IV colorectal cancer to FOLFIRI with or without cetuximab. The addition of cetuximab was associated with an improved PFS (HR, 0.85; 95% CI, 0.72–0.99, P = .048 by a stratified log rank test), but not OS.[Level of Evidence: 1iiDii] Retrospective studies of patients with metastatic colorectal cancer have suggested that responses to anti-epidermal growth factor receptor (EGFR) antibody therapy are confined to patients with tumors that harbor wild types of KRAS (i.e., lack activating mutations at code on 12 or 13 of the KRAS gene). A subset analysis evaluating efficacy vis a vis KRAS status was done in patients enrolled on the Crystal Study. There was a significant interaction for KRAS mutation status and treatment for tumor response (P = .03) but not for PFS (P = .07). Among KRAS wild-type patients, the HR favored the FOLFIRI/cetuximab group (HR, 0.68; 95% CI, 0.50–0.94).
Importantly, patients with mutant KRAS tumors may experience worse outcome when cetuximab is added to multiagent chemotherapy regimens containing bevacizumab. In a randomized trial, patients with metastatic colorectal cancer received capecitabine/oxaliplatin/bevacizumab with or without cetuximab. The median PFS was 9.4 months in the group receiving cetuximab and 10.7 months in the group not receiving cetuximab (P = .01). In a subset analysis, cetuximab-treated patients with tumors bearing a mutated KRAS gene had significantly decreased PFS compared with cetuximab-treated patients with wild type KRAS tumors (8.1 mo. vs. 10.5 mo.; P = .04). Cetuximab-treated patients with mutated KRAS tumors had a significantly shorter PFS compared with patients with mutated KRAS tumors not receiving cetuximab (8.1 mo. vs. 12.5 mo.; P = .003) as well as OS (17.2 months vs. 24.9 months; P = .03).[Level of evidence: 1iiDiii]
Panitumumab is a fully humanized antibody against the EGFR. In a phase III trial that has not yet been reported, patients with chemotherapy-refractory colorectal cancer were randomly assigned to panitumumab or best supportive care. Patients receiving panitumumab experienced improved OS. Despite the preliminary nature of this study, the FDA approved panitumumab for use in patients with metastatic colorectal cancer refractory to chemotherapy.