Derek J. Jonker, M.D., Chris J. O'Callaghan, Ph.D., Christos S. Karapetis, M.D., John R. Zalcberg, M.D., Dongsheng Tu, Ph.D., Heather-Jane Au, M.D., Scott R. Berry, M.D., Marianne Krahn, M.D., Timothy Price, M.D., R. John Simes, M.D., Niall C. Tebbutt, M.D., Guy van Hazel, M.D., Rafal Wierzbicki, M.D., Christiane Langer, M.D., and Malcolm J. Moore, M.D.
Background Cetuximab, an IgG1 chimeric monoclonal antibody againstepidermal growth factor receptor (EGFR), has activity againstcolorectal cancers that express EGFR.
Methods From December 2003 to August 2005, 572 patients whohad colorectal cancer expressing immunohistochemically detectableEGFR and who had been previously treated with a fluoropyrimidine,irinotecan, and oxaliplatin or had contraindications to treatmentwith these drugs underwent randomization to an initial doseof 400 mg of cetuximab per square meter of body-surface areafollowed by a weekly infusion of 250 mg per square meter plusbest supportive care (287 patients) or best supportive carealone (285 patients). The primary end point was overall survival.
Results In comparison with best supportive care alone, cetuximabtreatment was associated with a significant improvement in overallsurvival (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 afteradjustment in a multivariable Cox proportional-hazards model.The median overall survival was 6.1 months in the cetuximabgroup and 4.6 months in the group assigned to supportive carealone. Partial responses occurred in 23 patients (8.0%) in thecetuximab group but in none in the group assigned to supportivecare alone (P<0.001); the disease was stable in an additional31.4% of patients assigned to cetuximab and in 10.9% of patientsassigned to supportive care alone (P<0.001). Quality of lifewas better preserved in the cetuximab group, with less deteriorationin 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 improvedsurvival (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 orhigher was 78.5% in the cetuximab group and 59.1% in the groupassigned to supportive care alone (P<0.001).
Conclusions Cetuximab improves overall survival and progression-freesurvival and preserves quality-of-life measures in patientswith colorectal cancer in whom other treatments have failed.(ClinicalTrials.gov number, NCT00079066
[ClinicalTrials.gov]
.)
Source Information
From Ottawa Hospital Research Institute, University of Ottawa, Ottawa (D.J.J.); National Cancer Institute of Canada Clinical Trials Group, Queen's University, Kingston, ON (C.J.O., D.T.); Flinders Medical Centre, Adelaide, Australia (C.S.K.); Peter MacCallum Cancer Centre and Department of Medicine, University of Melbourne, Melbourne, Australia (J.R.Z.); Cross Cancer Institute, Edmonton, AB, Canada (H.-J.A.); Toronto–Sunnybrook Regional Cancer Centre, Toronto (S.R.B.); St. Boniface General Hospital, Winnipeg, MB, Canada (M.K.); Queen Elizabeth Hospital, Adelaide, Australia (T.P.); National Health and Medical Research Council Clinical Trials Centre, University of Sydney, Sydney (R.J.S.); Austin Health, Melbourne, Australia (N.C.T.); Sir Charles Gairdner Hospital, Perth, Australia (G.H.); Lakeridge Health, Oshawa, ON, Canada (R.W.); Bristol-Myers Squibb, Wallingford, CT (C.L.); and Princess Margaret Hospital, Toronto (M.J.M.). Drs. Jonker and O'Callaghan contributed equally to this article.
Address reprint requests to Dr. Jonker at the Ottawa Hospital Regional Cancer Centre, University of Ottawa, 501 Smyth Rd., Box 912, Ottawa, ON K1H 8L6, Canada, or at djonker{at}ottawahospital.on.ca.
Cetuximab for Colorectal Cancer
Yang F., Fu D., Ni Q., Fraggetta F., Pelosi G., Roila F., Garassino M. C., Mantica C., van der Spek E., Sonke G. S., Jonker D. J., O'Callaghan C. J.
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N Engl J Med 2008;
358:1195-1197, Mar 13, 2008.
Correspondence
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