This Article Full Text Full Text (PDF) Purchase Article View Shopping Cart Alert me when this article is cited Alert me if a correction is posted Services Email this article to a colleague Similar articles in this journal Similar articles in PubMed Alert me to new issues of the journal Save to my personal folders Download to citation manager Citing Articles Citing Articles via HighWire Google Scholar Articles by Lièvre, A. Articles by Laurent-Puig, P. PubMed PubMed Citation Articles by Lièvre, A. Articles by Laurent-Puig, P. Related Articles Related Correspondence

KRAS Mutations As an Independent Prognostic Factor in Patients With Advanced Colorectal Cancer Treated With Cetuximab

Astrid Lièvre, 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

From the L'Institut National de la Santé et de la Recherche Médicale; Université Paris-Descartes; Assistance Publique–Hôpitaux de Paris, Hôpital Européen Georges Pompidou; Assistance Publique–Hôpitaux de Paris, Hôpital Saint-Antoine; Assistance Publique–Hôpitaux de Paris, Hôpital Tenon, Paris; Assistance Publique–Hôpitaux de Paris, Hôpital Ambroise Paré, Boulogne-Billancourt; Université de Versailles Saint-Quentin-en-Yvelines, Versailles; Institut Gustave Roussy, Villejuif; Centre Jean Perrin; Université Auvergne; Centre Hospitalier Universitaire (CHU) Clermont-Ferrand, Service Chirurgie Digestive, Clermont-Ferrand; Centre Val d'Aurelle, Montpellier; and CHU Robert Debré, Reims, France

Corresponding author: Pierre Laurent-Puig, MD, PhD, L'Institut National de la Santé et de la Recherche Médicale U775, Université Paris-Descartes, 45 rue des Saints-Pères, 75006 Paris, France; e-mail: pierre.laurent-puig{at}univ-paris5.fr

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.

Supported by the Ligue Nationale de Lutte Contre le Cancer and the Institut National du Cancer (PL06_119).

Authors’ disclosures of potential conflicts of interest and author contributions are found at the end of this article.

Related Correspondence

• Should KRAS Mutations Be Considered an Independent Prognostic Factor in Patients With Advanced Colorectal Cancer Treated With Cetuximab?
  Marina Chiara Garassino, Gabriella Farina, Antonio Rossi, Olga Martelli, and Valter Torri
  JCO 2008 26: 2600 [Full Text]

This article has been cited by other articles:

				B. Vincenzi, D. Santini, S. Galluzzo, A. Russo, F. Fulfaro, M. Silletta, F. Battistoni, L. Rocci, B. B. Zobel, V. Adamo, et al. Early Magnesium Reduction in Advanced Colorectal Cancer Patients Treated with Cetuximab Plus Irinotecan as Predictive Factor of Efficacy and Outcome Clin. Cancer Res., July 1, 2008; 14(13): 4219 - 4224. [Abstract] [Full Text] [PDF]

				M. C. Garassino, G. Farina, A. Rossi, O. Martelli, and V. Torri Should KRAS Mutations Be Considered an Independent Prognostic Factor in Patients With Advanced Colorectal Cancer Treated With Cetuximab? J. Clin. Oncol., May 20, 2008; 26(15): 2600 - 2600. [Full Text] [PDF]

				A. Lievre and P. Laurent-Puig In Reply J. Clin. Oncol., May 20, 2008; 26(15): 2601 - 2602. [Full Text] [PDF]

				Cetuximab Therapy Is Inactive in Colorectal Cancer Patients with KRAS Mutations Journal Watch Oncology and Hematology, February 19, 2008; 2008(219): 3 - 3. [Full Text]