Fluorouracil, leucovorin, and oxaliplatin with and without cetuximab in the first-line treatment of metastatic colorectal cancer

Carsten Bokemeyer, Igor Bondarenko, Anatoly Makhson, Joerg T. Hartmann, Jorge Aparicio, Filippo De Braud, Serban Donea, Heinz Ludwig, Gunter Schuch, Christopher Stroh, Anja H. Loos, Angela Zubel, Piotr Koralewski

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Abstract

Purpose This randomized study assessed whether the best overall response rate (ORR) of cetuximab combined with oxaliplatin, leucovorin, and fluorouracil (FOLFOX-4) was superior to that of FOLFOX-4 alone as first-line treatment for metastatic colorectal cancer. The influence of KRAS mutation status was investigated. Patients and Methods Patients received cetuximab (400 mg/m 2 initial dose followed by 250 mg/m2/wk thereafter) plus FOLFOX-4 (oxaliplatin 85 mg/m2 on day 1, plus leucovorin 200 mg/m2 and fluorouracil as a 400 mg/m2 bolus followed by a 600 mg/m2 infusion during 22 hours on days 1 and 2; n = 169) or FOLFOX-4 alone (n = 168). Treatment was continued until disease progression or unacceptable toxicity. KRAS mutation status was assessed in the subset of patients with assessable tumor samples (n = 233). Results The confirmed ORR for cetuximab plus FOLFOX-4 was higher than with FOLFOX-4 alone (46% v 36%). A statistically significant increase in the odds for a response with the addition of cetuximab to FOLFOX-4 could not be established (odds ratio = 1.52; P = .064). In patients with KRAS wild-type tumors, the addition of cetuximab to FOLFOX-4 was associated with a clinically significant increased chance of response (ORR = 61% v 37%; odds ratio = 2.54; P = .011) and a lower risk of disease progression (hazard ratio = 0.57; P = .0163) compared with FOLFOX-4 alone. Cetuximab plus FOLFOX-4 was generally well tolerated. Conclusion KRAS mutational status was shown to be a highly predictive selection criterion in relation to the treatment decision regarding the addition of cetuximab to FOLFOX-4 for previously untreated patients with metastatic colorectal cancer.

Original languageEnglish
Pages (from-to)663-671
Number of pages9
JournalJournal of Clinical Oncology
Volume27
Issue number5
DOIs
Publication statusPublished - Feb 10 2009

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ASJC Scopus subject areas

  • Cancer Research
  • Oncology

Cite this

Bokemeyer, C., Bondarenko, I., Makhson, A., Hartmann, J. T., Aparicio, J., De Braud, F., Donea, S., Ludwig, H., Schuch, G., Stroh, C., Loos, A. H., Zubel, A., & Koralewski, P. (2009). Fluorouracil, leucovorin, and oxaliplatin with and without cetuximab in the first-line treatment of metastatic colorectal cancer. Journal of Clinical Oncology, 27(5), 663-671. https://doi.org/10.1200/JCO.2008.20.8397