Annals of Oncology Advance Access published online on November 12, 2007
Annals of Oncology, doi:10.1093/annonc/mdm496
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© 2007 European Society for Medical Oncology
KRAS wild-type state predicts survival and is associated to early radiological response in metastatic colorectal cancer treated with cetuximab
1 Center for Human Genetics, Katholieke Universiteit Leuven, Leuven
2 Service de Gastro-entérologie, Cliniques universitaires Saint-Luc, Université catholique de Louvain, Brussels
3 Independent biostatistician, Mechelen
4 Department of Morphology and Molecular Pathology University Hospital Gasthuisberg, Katholieke Universiteit Leuven, Leuven
5 Digestive Oncology Unit, University Hospital Gasthuisberg, Katholieke Universiteit Leuven, Leuven
6 Department of Gastroenterology, Gastro-Intestinal Cancer Unit, Erasme University Hospital, Université Libre de Bruxelles, Brussels
7 Digestive Oncology Unit, Ghent University Hospital, Ghent
8 Clinique des Pathologies Tumorales du Côlon et du Rectum, Centre du Cancer, Cliniques universitaires Saint-Luc, Université catholique de Louvain, Brussels, Belgium
* Correspondence to: Prof. S. Tejpar, Digestive Oncology Unit, University Hospital Gasthuisberg, Herestraat 49, 3000 Leuven, Belgium. Tel: +32-16-344218; Fax: +32-16-344419; E-mail: sabine.tejpar{at}uz.kuleuven.be
Background: KRAS mutation status is a candidate marker for predicting survival in patients with metastatic colorectal cancer (mCRC) treated with cetuximab (CTX).
Patients and methods: We studied the KRAS mutation status of 113 patients with irinotecan refractory mCRC treated with CTX in clinical trials. A predictive model for objective response (OR), progression-free survival (PFS) and overall survival (OS) was constructed using logistic and Cox regression.
Results: OR was seen in 27 of 66 KRAS wild-type (WT) patients versus 0 of 42 in KRAS mutants. Median OS was significantly better in KRAS WT versus mutants (43.0 versus 27.3 weeks; P = 0.020). Decrease in tumor sizes was significantly larger at all time points in WT patients. KRAS WT patients with an initial relative decrease of tumor size >9.66% at week 6 had a significantly better median OS compared with all other patients (74.9 versus 30.6 weeks; P = 0.0000025). Within KRAS WT patients OS was significantly better in patients with an initial decrease compared with those without [median OS: 74.9 versus 30.6 weeks (P = 0.00000012)].
Conclusions: KRAS WT status is associated to survival benefit in CTX treated mCRC. This benefit is even more pronounced in those patients with early radiological response. These characteristics may be exploited for response prediction.
cetuximab, colorectal cancer, EGFR, KRAS, survival
Received for publication June 26, 2007. Revision received September 12, 2007. Accepted for publication September 14, 2007.
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