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Previous Volume 360:1408-1417 April 2, 2009 Number 14 Next

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ABSTRACT

Background We investigated the efficacy of cetuximab plus irinotecan, fluorouracil, and leucovorin (FOLFIRI) as first-line treatment for metastatic colorectal cancer and sought associations between the mutation status of the KRAS gene in tumors and clinical response to cetuximab.

Methods We randomly assigned patients with epidermal growth factor receptor–positive colorectal cancer with unresectable metastases to receive FOLFIRI either alone or in combination with 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-free survival in the cetuximab–FOLFIRI group as compared with the FOLFIRI group was 0.85 (95% confidence interval [CI], 0.72 to 0.99; P=0.048). There was no significant difference in the overall survival between the two treatment groups (hazard ratio, 0.93; 95% CI, 0.81 to 1.07; P=0.31). There was a significant interaction between treatment group and KRAS mutation status for tumor response (P=0.03) but not for progression-free survival (P=0.07) or overall survival (P=0.44). The hazard ratio for progression-free survival among patients with wild-type–KRAS tumors was 0.68 (95% CI, 0.50 to 0.94), in favor of the cetuximab–FOLFIRI group. The following grade 3 or 4 adverse events were more frequent with 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), and diarrhea (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 progression of metastatic colorectal cancer. The benefit of cetuximab was limited to patients with KRAS wild-type tumors. (ClinicalTrials.gov number, 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.

Full Text of this Article

Related Letters:

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.
Extract | Full Text | PDF  
N Engl J Med 2009; 361:95-97, Jul 2, 2009. Correspondence

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