KRAS mutations as an independent prognostic factor in patients with advanced colorectal cancer treated with cetuximab - PubMed (original) (raw)

Multicenter Study

. 2008 Jan 20;26(3):374-9.

doi: 10.1200/JCO.2007.12.5906.

Jean-Baptiste Bachet, Valérie Boige, Anne Cayre, Delphine Le Corre, Emmanuel Buc, Marc Ychou, Olivier Bouché, Bruno Landi, Christophe Louvet, Thierry André, Fréderic Bibeau, Marie-Danièle Diebold, Philippe Rougier, Michel Ducreux, Gorana Tomasic, Jean-François Emile, Frédérique Penault-Llorca, Pierre Laurent-Puig

Affiliations

Multicenter Study

KRAS mutations as an independent prognostic factor in patients with advanced colorectal cancer treated with cetuximab

Astrid Lièvre et al. J Clin Oncol. 2008.

Abstract

Purpose: Cetuximab is efficient in advanced colorectal cancer (CRC). We previously showed that KRAS mutations were associated with resistance to cetuximab in 30 CRC patients. The aim of this study was to validate, in an independent larger series of 89 patients, the prognostic value of KRAS mutations on response to cetuximab and survival.

Patients and methods: Eighty-nine metastatic CRC patients treated with cetuximab after treatment failure with irinotecan-based chemotherapy were analyzed for KRAS mutation by allelic discrimination on tumor DNA. The association between KRAS mutations and tumor response, skin toxicity, progression-free survival (PFS) and overall survival (OS) was analyzed.

Results: A KRAS mutation was present in 27% of the patients and was associated with resistance to cetuximab (0% v 40% of responders among the 24 mutated and 65 nonmutated patients, respectively; P < .001) and a poorer survival (median PFS: 10.1 v 31.4 weeks in patients without mutation; P = .0001; median OS: 10.1 v 14.3 months in patients without mutation; P = .026). When we pooled these 89 patients with patients from our previous study, the multivariate analysis showed that KRAS status was an independent prognostic factor associated with OS and PFS, whereas skin toxicity was only associated with OS. In a combined analysis, median OS times of patients with two, one, or no favorable prognostic factors (severe skin toxicity and no KRAS mutation) was of 15.6, 10.7, and 5.6 months, respectively.

Conclusion: These results confirm the high prognostic value of KRAS mutations on response to cetuximab and survival in metastatic CRC patients treated with cetuximab.

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