EGFR expression is often increased in colorectal cancer. The chimeric IgG1 monoclonal antibody against EGFR, cetuximab, has demonstrated activity against colorectal cancer and when administered with irinotecan can reverse drug resistance in patients with colorectal cancer.OBJETIVE
To investigate the effect of cetuximab on survival and quality of life in patients with advanced colorectal cancer.DESIGN AND INTERVENTION
Patients with advanced colorectal cancer and EGFR overexpression detectable by immunohistochemistry who had not responded to previous treatment with a fluoropyrimidine, irinotecan and oxaliplatin were eligible for inclusion in the study. Patients who had received treatment with a murine monoclonal antibody or any agent that targets the EGFR pathway were ineligible. A total of 572 eligible patients were randomized to receive either treatment with intravenous cetuximab - at an initial dose of 400 mg/m2 for a period of 120 min, followed by a weekly maintenance dose of 250 mg/m2 for a period of 60 min plus best supportive care (n = 287) - or best supportive care alone (n = 285). Best supportive care was designed to improve quality of life and provide optimum palliation of symptoms.OUTCOME MEASURES
The primary end point was overall survival (OS). Secondary end points included progression - free survival (PFS), response rates and quality of life.RESULTS
Cetuximab plus supportive care resulted in significantly improved OS (hazard ratio [HR] for death 0.77, 95% CI 0.64-0.92; P = 0.005) and PFS (HR for disease progression or death 0.68, 95% CI 0.57-0.80; P < 0.001) compared with best supportive care alone. Median survival was 6.1 months in the cetuximab group and 4.6 months in the supportive-care group. At 6 and 12 months, respectively, the proportion of patients surviving was 50% and 21% in the cetuximab group and 33% and 16% in the supportive-care group. Partial responses were experienced by 23 patients in the cetuximab group but by none of the patients in the best-supportive-care group. Deteriorations in physical function and in global health status were lower in those treated with cetuximab. The incidence of grade 3 or higher rash was significantly greater in patients treated with cetuximab than in those receiving supportive care only (11.8% vs 0.4%; P < 0.001). Notably, a rash of grade 2 or higher was related to improved survival (HR for death 0.33, 95% CI 0.22-0.50; P < 0.001). The occurrence of any adverse event (grade 3 or higher) was higher in the cetuximab group (78.5%) than in the supportive-care group (59.1%; P < 0.001).CONCLUSION
Treatment with cetuximab improves OS and PFS and conserves quality of life in patients with colorectal cancer who have received prior treatment.