Clinical Study

BJC Open article

British Journal of Cancer (2007) 96, 1166–1169. doi:10.1038/sj.bjc.6603685 www.bjcancer.com
Published online 20 March 2007

Clinical relevance of KRAS mutation detection in metastatic colorectal cancer treated by Cetuximab plus chemotherapy

F Di Fiore1, F Blanchard3, F Charbonnier2, F Le Pessot2,3, A Lamy3, M P Galais4, L Bastit5, A Killian2, R Sesboüé2, J J Tuech2,6, A M Queuniet7, B Paillot1, J C Sabourin2,3, F Michot2,6, P Michel1 and T Frebourg2

  1. 1Digestive Oncology Unit, Department of Hepato-Gastroenterology, Rouen University Hospital, Northwest Canceropole, France and Inserm U614, Faculty of Medicine, Northwest Canceropole, Rouen, France
  2. 2Inserm U614, Faculty of Medicine, Northwest Canceropole, Rouen, France
  3. 3Department of Pathology, Rouen University Hospital, Northwest Canceropole, France
  4. 4Digestive Oncology Unit, Department of Hepato-Gastroenterology, Caen University Hospital and Francois Baclesse Centre, Caen, Northwest Canceropole, France
  5. 5Oncology Unit, St Hilaire Medical Centre, Rouen, France
  6. 6Department of Surgery, Rouen University Hospital, Northwest Canceropole, France
  7. 7Digestive Oncology Unit, Department of Hepato-Gastroenterology, Elbeuf Hospital, France

Correspondence: Dr F Di Fiore, E-mail: frederic.di-fiore@chu-rouen.fr

Received 23 October 2006; Revised 19 February 2007; Accepted 19 February 2007
Advance online publication 20 March 2007

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Abstract

The predictive value of KRAS mutation in metastatic colorectal cancer (MCRC) patients treated with cetuximab plus chemotherapy has recently been suggested. In our study, 59 patients with a chemotherapy-refractory MCRC treated with cetuximab plus chemotherapy were included and clinical response was evaluated according to response evaluation criteria in solid tumours (RECIST). Tumours were screened for KRAS mutations using first direct sequencing, then two sensitive methods based on SNaPshot and PCR-ligase chain reaction (LCR) assays. Clinical response was evaluated according to gene mutations using the Fisher exact test. Times to progression (TTP) were calculated using the Kaplan–Meier method and compared with log-rank test. A KRAS mutation was detected in 22 out of 59 tumours and, in six cases, was missed by sequencing analysis but detected using the SNaPshot and PCR-LCR assays. Remarkably, no KRAS mutation was found in the 12 patients with clinical response. KRAS mutation was associated with disease progression (P=0.0005) and TTP was significantly decreased in mutated KRAS patients (3 vs 5.5 months, P=0.015). Our study confirms that KRAS mutation is highly predictive of a non-response to cetuximab plus chemotherapy in MCRC and highlights the need to use sensitive molecular methods, such as SNaPshot or PCR-LCR assays, to ensure an efficient mutation detection.

Keywords:

colorectal cancer; EGFR; KRAS; molecular markers; mutation

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