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Previous Volume 360:563-572 February 5, 2009 Number 6 Next

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ABSTRACT

Background Fluoropyrimidine-based chemotherapy plus the anti–vascular endothelial growth factor (VEGF) antibody bevacizumab is standard first-line treatment for metastatic colorectal cancer. We studied the effect of adding the anti–epidermal growth factor receptor (EGFR) antibody cetuximab to a combination of capecitabine, oxaliplatin, and bevacizumab for metastatic colorectal cancer.

Methods We randomly assigned 755 patients with previously untreated metastatic colorectal cancer to capecitabine, oxaliplatin, and bevacizumab (CB regimen, 378 patients) or the same regimen plus weekly cetuximab (CBC regimen, 377 patients). The primary end point was progression-free survival. The mutation status of the KRAS gene was evaluated as a predictor of outcome.

Results The median progression-free survival was 10.7 months in the CB group and 9.4 in the CBC group (P=0.01). Quality-of-life scores were lower in the CBC group. The overall survival and response rates did not differ significantly in the two groups. Treated patients in the CBC group had more grade 3 or 4 adverse events, which were attributed to cetuximab-related adverse cutaneous effects. Patients treated with cetuximab who had tumors bearing a mutated KRAS gene had significantly decreased progression-free survival as compared with cetuximab-treated patients with wild-type–KRAS tumors or patients with mutated-KRAS tumors in the CB group.

Conclusions The addition of cetuximab to capecitabine, oxaliplatin, and bevacizumab resulted in significantly shorter progression-free survival and inferior quality of life. Mutation status of the KRAS gene was a predictor of outcome in the cetuximab group. (ClinicalTrials.gov number, NCT00208546 [ClinicalTrials.gov] .)

Source Information

From Radboud University Nijmegen Medical Center, Nijmegen (J.T., M.K., J.R.D., M.E.V.-B., J.H.J.M.K., C.J.A.P.); the Netherlands Cancer Institute, Amsterdam (A.C., N.F.A., O.D.); Meander Medical Center, Amersfoort (C.J.R.); Catharina Hospital, Eindhoven (G.J.M.C.); Spaarne Hospital, Hoofddorp (J.G.S.); Maasland Hospital, Sittard (F.L.G.E.); Bernhoven Hospital, Oss (A.H.V.); the Free University Medical Center, Amsterdam (C.J.G.); Jeroen Bosch Hospital, `s-Hertogenbosch (H.A.M.S.); the Amsterdam Medical Center, Amsterdam (D.J.R.); University Medical Center, Utrecht (E.E.V.); and the Comprehensive Cancer Center East, Nijmegen (L.M.) — all in the Netherlands.

Address reprint requests to Dr. Punt at the Department of Medical Oncology, Radboud University Nijmegen Medical Center, P.O. Box 9101, 6500 HB Nijmegen, the Netherlands, or at c.punt{at}onco.umcn.nl.

Full Text of this Article

Related Letters:

Chemotherapy and Immunotherapy in Metastatic Colorectal Cancer
Pohlmann P. R., Mernaugh R. L., Goff L. W., Frati L., Codacci-Pisanelli G., Copur M. S., Norvell M., Obermiller A., Loupakis F., Di Maio M., Falcone A., Punt C. J.A., Tol J.
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N Engl J Med 2009; 360:2134-2136, May 14, 2009. Correspondence

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