• J. Clin. Oncol. · May 2011

    Randomized Controlled Trial Multicenter Study

    Cetuximab plus irinotecan, fluorouracil, and leucovorin as first-line treatment for metastatic colorectal cancer: updated analysis of overall survival according to tumor KRAS and BRAF mutation status.

    • Eric Van Cutsem, Claus-Henning Köhne, István Láng, Gunnar Folprecht, Marek P Nowacki, Stefano Cascinu, Igor Shchepotin, Joan Maurel, David Cunningham, Sabine Tejpar, Michael Schlichting, Angela Zubel, Ilhan Celik, Philippe Rougier, and Fortunato Ciardiello.
    • University Hospital Gasthuisberg, Herestraat 49, 3000 Leuven, Belgium. eric.vancutsem@uz.kuleuven.ac.be
    • J. Clin. Oncol. 2011 May 20; 29 (15): 2011-9.

    PurposeThe addition of cetuximab to irinotecan, fluorouracil, and leucovorin (FOLFIRI) as first-line treatment for metastatic colorectal cancer (mCRC) was shown to reduce the risk of disease progression and increase the chance of response in patients with KRAS wild-type disease. An updated survival analysis, including additional patients analyzed for tumor mutation status, was undertaken.Patients And MethodsPatients were randomly assigned to receive FOLFIRI with or without cetuximab. DNA was extracted from additional slide-mounted tumor samples previously used to assess epidermal growth factor receptor expression. Clinical outcome according to the tumor mutation status of KRAS and BRAF was assessed in the expanded patient series.ResultsThe ascertainment rate of patients analyzed for tumor KRAS status was increased from 45% to 89%, with mutations detected in 37% of tumors. The addition of cetuximab to FOLFIRI in patients with KRAS wild-type disease resulted in significant improvements in overall survival (median, 23.5 v 20.0 months; hazard ratio [HR], 0.796; P = .0093), progression-free survival (median, 9.9 v 8.4 months; HR, 0.696; P = .0012), and response (rate 57.3% v 39.7%; odds ratio, 2.069; P < .001) compared with FOLFIRI alone. Significant interactions between KRAS status and treatment effect were noted for all key efficacy end points. KRAS mutation status was confirmed as a powerful predictive biomarker for the efficacy of cetuximab plus FOLFIRI. BRAF tumor mutation was a strong indicator of poor prognosis.ConclusionThe addition of cetuximab to FOLFIRI as first-line therapy improves survival in patients with KRAS wild-type mCRC. BRAF tumor mutation is an indicator of poor prognosis.

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