Cetuximab for the treatment of colorectal cancer.
BACKGROUND
Cetuximab, an IgG1 chimeric monoclonal antibody against epidermal growth factor receptor (EGFR), has activity against colorectal cancers that express EGFR.


METHODS
From December 2003 to August 2005, 572 patients who had colorectal cancer expressing immunohistochemically detectable EGFR and who had been previously treated with a fluoropyrimidine, irinotecan, and oxaliplatin or had contraindications to treatment with these drugs underwent randomization to an initial dose of 400 mg of cetuximab per square meter of body-surface area followed by a weekly infusion of 250 mg per square meter plus best supportive care (287 patients) or best supportive care alone (285 patients). The primary end point was overall survival.


RESULTS
In comparison with best supportive care alone, cetuximab treatment was associated with a significant improvement in overall survival (hazard ratio for death, 0.77; 95% confidence interval [CI], 0.64 to 0.92; P=0.005) and in progression-free survival (hazard ratio for disease progression or death, 0.68; 95% CI, 0.57 to 0.80; P<0.001). These benefits were robust after adjustment in a multivariable Cox proportional-hazards model. The median overall survival was 6.1 months in the cetuximab group and 4.6 months in the group assigned to supportive care alone. Partial responses occurred in 23 patients (8.0%) in the cetuximab group but in none in the group assigned to supportive care alone (P<0.001); the disease was stable in an additional 31.4% of patients assigned to cetuximab and in 10.9% of patients assigned to supportive care alone (P<0.001). Quality of life was better preserved in the cetuximab group, with less deterioration in physical function and global health status scores (both P<0.05). Cetuximab treatment was associated with a characteristic rash; a rash of grade 2 or higher was strongly associated with improved survival (hazard ratio for death, 0.33; 95% CI, 0.22 to 0.50; P<0.001). The incidence of any adverse event of grade 3 or higher was 78.5% in the cetuximab group and 59.1% in the group assigned to supportive care alone (P<0.001).


CONCLUSIONS
Cetuximab improves overall survival and progression-free survival and preserves quality-of-life measures in patients with colorectal cancer in whom other treatments have failed. (ClinicalTrials.gov number, NCT00079066 [ClinicalTrials.gov].).
Jonker
Derek J
DJ
Ottawa Hospital Research Institute, University of Ottawa, Ottawa, ON, Canada. djonker@ottawahospital.on.ca
O'Callaghan
Chris J
CJ
Karapetis
Christos S
CS
Zalcberg
John R
JR
Tu
Dongsheng
D
Au
Heather-Jane
HJ
Berry
Scott R
SR
Krahn
Marianne
M
Price
Timothy
T
Simes
R John
RJ
Tebbutt
Niall C
NC
van Hazel
Guy
G
Wierzbicki
Rafal
R
Langer
Christiane
C
Moore
Malcolm J
MJ
D000328:Adult; D000368:Aged; D000369:Aged, 80 and over; D000911:Antibodies, Monoclonal / Q000009:adverse effects / Q000627:therapeutic use*; D061067:Antibodies, Monoclonal, Humanized; D000970:Antineoplastic Agents / Q000009:adverse effects / Q000627:therapeutic use*; D000068818:Cetuximab; D015179:Colorectal Neoplasms / Q000188:drug therapy* / Q000401:mortality; D066246:ErbB Receptors / Q000276:immunology*; D005076:Exanthema / Q000139:chemically induced; D005260:Female; D006801:Humans; D007262:Infusions, Intravenous; D008297:Male; D008875:Middle Aged; D016019:Survival Analysis
D000911:Antibodies, Monoclonal; D061067:Antibodies, Monoclonal, Humanized; D000970:Antineoplastic Agents; D066246:ErbB Receptors; D000068818:Cetuximab