KRAS wild-type state predicts survival and is associated to early radiological response in metastatic colorectal cancer treated with cetuximab

被引:687
作者
De Roock, W. [2 ]
Piessevaux, H. [3 ]
De Schutter, J. [2 ]
Janssens, M.
De Hertogh, G. [4 ]
Personeni, N. [1 ]
Biesmans, B. [2 ]
Van Laethem, J. -L. [5 ]
Peeters, M. [6 ]
Humblet, Y. [7 ]
Van Cutsem, E. [1 ]
Tejpar, S. [1 ]
机构
[1] Katholieke Univ Leuven, Univ Hosp Gasthuisberg, Digest Oncol Unit, B-3000 Louvain, Belgium
[2] Katholieke Univ Leuven, Ctr Human Genet, Louvain, Belgium
[3] Catholic Univ Louvain, Clin Univ St Luc, Serv Gastroenterol, Brussels, Belgium
[4] Katholieke Univ Leuven, Univ Hosp Gasthuisberg, Dept Morphol & Mol Pathol, Louvain, Belgium
[5] Univ Libre Bruxelles, Erasme Univ Hosp, Gastrointestinal Canc Unit, Dept Gastroenterol, Brussels, Belgium
[6] Ghent Univ Hosp, Digest Oncol Unit, B-9000 Ghent, Belgium
[7] Catholic Univ Louvain, Clin Univ St Luc, Ctr Canc, Clin Pathol Tumorales Colon & Rectum, Brussels, Belgium
关键词
cetuximab; colorectal cancer; EGFR; KRAS; survival;
D O I
10.1093/annonc/mdm496
中图分类号
R73 [肿瘤学];
学科分类号
100214 ;
摘要
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.
引用
收藏
页码:508 / 515
页数:8
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