Background We investigated the efficacy of cetuximab plus irinotecan,fluorouracil, and leucovorin (FOLFIRI) as first-line treatmentfor metastatic colorectal cancer and sought associations betweenthe mutation status of the KRAS gene in tumors and clinicalresponse to cetuximab.
Methods We randomly assigned patients with epidermal growthfactor receptor–positive colorectal cancer with unresectablemetastases to receive FOLFIRI either alone or in combinationwith cetuximab. The primary end point was progression-free survival.
Results A total of 599 patients received cetuximab plus FOLFIRI,and 599 received FOLFIRI alone. The hazard ratio for progression-freesurvival in the cetuximab–FOLFIRI group as compared withthe FOLFIRI group was 0.85 (95% confidence interval [CI], 0.72to 0.99; P=0.048). There was no significant difference in theoverall survival between the two treatment groups (hazard ratio,0.93; 95% CI, 0.81 to 1.07; P=0.31). There was a significantinteraction between treatment group and KRAS mutation statusfor tumor response (P=0.03) but not for progression-free survival(P=0.07) or overall survival (P=0.44). The hazard ratio forprogression-free survival among patients with wild-type–KRAStumors was 0.68 (95% CI, 0.50 to 0.94), in favor of the cetuximab–FOLFIRIgroup. The following grade 3 or 4 adverse events were more frequentwith cetuximab plus FOLFIRI than with FOLFIRI alone: skin reactions(which were grade 3 only) (in 19.7% vs. 0.2% of patients, P<0.001),infusion-related reactions (in 2.5% vs. 0%, P<0.001), anddiarrhea (in 15.7% vs. 10.5%, P=0.008).
Conclusions First-line treatment with cetuximab plus FOLFIRI,as compared with FOLFIRI alone, reduced the risk of progressionof metastatic colorectal cancer. The benefit of cetuximab waslimited to patients with KRAS wild-type tumors. (ClinicalTrials.govnumber, NCT00154102
[ClinicalTrials.gov]
.)
Source Information
From the University Hospital Gasthuisberg, Leuven (E.V.C., S.T.); and Imelda Ziekenhuis, Bonheiden (G.D.) — both in Belgium; Klinikum Oldenburg, Oldenburg (C.-H.K.); Universitätsklinikum Carl Gustav Carus, Dresden (G.F.); and Merck, Darmstadt (C.S., M.S., J.N.) — all in Germany; Országos Onkológiai Intézet, Budapest (E.H.); Petz Aladár County Teaching Hospital, Gyr (T.P.); and St. László Hospital, Budapest (G.B.) — all in Hungary; Wielkopolskie Centrum Onkologii, Poznan, Poland (J.Z.); Chang Gung Memorial Hospital, Taoyuan, Taiwan (C.-R.C.C.); Moscow City Oncology Clinical Hospital 62, Moscow (A.M.); National University Hospital, Singapore, Singapore (R.L.); Yonsei University College of Medicine, Seoul, South Korea (J.K.R.); University of Witwatersrand, Johannesburg, South Africa (P. Ruff); and Hôpital Ambroise Paré, Boulogne, France (P. Rougier).
Address reprint requests to Dr. Van Cutsem at the University Hospital Gasthuisberg, Digestive Oncology Unit, Herestraat 49, 3000 Leuven, Belgium, or at eric.vancutsem{at}uz.kuleuven.ac.be.
Cetuximab for Metastatic Colorectal Cancer
Spiro H., Roila F., Garassino M. C., Ballatori E., Bria E., Cuppone F., Di Maio M., Garattini S., Torri V., Floriani I., Van Cutsem E., Rougier P., Köhne C.-H.
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N Engl J Med 2009;
361:95-97, Jul 2, 2009.
Correspondence
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