Clinical relevance of KRAS mutation detection in metastatic colorectal cancer treated by Cetuximab plus chemotherapy
| Autor: | A. Lamy, Jean-Christophe Sabourin, Audrey Killian, Pierre Michel, Thierry Frebourg, L Bastit, F. Le Pessot, Bernard Paillot, Richard Sesboüé, F. Di Fiore, A.-M. Queuniet, Francis Michot, M.P. Galais, F. Blanchard, Jean-Jacques Tuech, Françoise Charbonnier |
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| Rok vydání: | 2007 |
| Předmět: |
Cancer Research
molecular markers Colorectal cancer EGFR medicine.medical_treatment colorectal cancer Antineoplastic Agents Gene mutation medicine.disease_cause Metastasis Clinical Studies KRAS medicine Humans Neoplasm Metastasis neoplasms Chemotherapy Cetuximab business.industry medicine.disease digestive system diseases ErbB Receptors KRAS Mutation Analysis Genes ras Oncology Mutation Monoclonal Cancer research Colorectal Neoplasms business medicine.drug |
| Zdroj: | British Journal of Cancer |
| ISSN: | 1532-1827 0007-0920 |
| DOI: | 10.1038/sj.bjc.6603685 |
| Popis: | 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. |
| Databáze: | OpenAIRE |
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