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

W. De Roock, H. Piessevaux, J. De Schutter, M. Janssens, G. De Hertogh, N. Personeni, B. Biesmans, J. L. Van Laethem, M. Peeters, Y. Humblet, E. Van Cutsem, Sabine Tejpar

Research output: Contribution to journalArticle

Abstract

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.

Original languageEnglish
Pages (from-to)508-515
Number of pages8
JournalAnnals of Oncology
Volume19
Issue number3
DOIs
Publication statusPublished - Mar 2008

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Colorectal Neoplasms
Survival
irinotecan
Cetuximab
Mutation
Disease-Free Survival
Neoplasms
Logistic Models
Clinical Trials

Keywords

  • Cetuximab
  • Colorectal cancer
  • EGFR
  • KRAS
  • Survival

ASJC Scopus subject areas

  • Oncology
  • Cancer Research

Cite this

KRAS wild-type state predicts survival and is associated to early radiological response in metastatic colorectal cancer treated with cetuximab. / De Roock, W.; Piessevaux, H.; De Schutter, J.; Janssens, M.; De Hertogh, G.; Personeni, N.; Biesmans, B.; Van Laethem, J. L.; Peeters, M.; Humblet, Y.; Van Cutsem, E.; Tejpar, Sabine.

In: Annals of Oncology, Vol. 19, No. 3, 03.2008, p. 508-515.

Research output: Contribution to journalArticle

De Roock, W, Piessevaux, H, De Schutter, J, Janssens, M, De Hertogh, G, Personeni, N, Biesmans, B, Van Laethem, JL, Peeters, M, Humblet, Y, Van Cutsem, E & Tejpar, S 2008, 'KRAS wild-type state predicts survival and is associated to early radiological response in metastatic colorectal cancer treated with cetuximab', Annals of Oncology, vol. 19, no. 3, pp. 508-515. https://doi.org/10.1093/annonc/mdm496
De Roock, W. ; Piessevaux, H. ; De Schutter, J. ; Janssens, M. ; De Hertogh, G. ; Personeni, N. ; Biesmans, B. ; Van Laethem, J. L. ; Peeters, M. ; Humblet, Y. ; Van Cutsem, E. ; Tejpar, Sabine. / KRAS wild-type state predicts survival and is associated to early radiological response in metastatic colorectal cancer treated with cetuximab. In: Annals of Oncology. 2008 ; Vol. 19, No. 3. pp. 508-515.
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AU - De Roock, W.

AU - Piessevaux, H.

AU - De Schutter, J.

AU - Janssens, M.

AU - De Hertogh, G.

AU - Personeni, N.

AU - Biesmans, B.

AU - Van Laethem, J. L.

AU - Peeters, M.

AU - Humblet, Y.

AU - Van Cutsem, E.

AU - Tejpar, Sabine

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AB - 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.

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