KRAS-mutated plasma DNA as predictor of outcome from irinotecan monotherapy in metastatic colorectal cancer

K. G. Spindler*, A. L. Appelt, N. Pallisgaard, R. F. Andersen, A. Jakobsen

*Corresponding author for this work

Research output: Contribution to journalJournal articlepeer-review

Abstract

Background:We investigated the clinical implications of KRAS and BRAF mutations detected in both archival tumor tissue and plasma cell-free DNA in metastatic colorectal cancer patients treated with irinotecan monotherapy.Methods:Two hundred and eleven patients receiving second-line irinotecan (350 mg m-2 q3w) were included in two independent cohorts. Plasma was obtained from pretreatment EDTA blood-samples. Mutations were detected in archival tumour and plasma with qPCR methods.Results:Mutation status in tumor did not correlate to efficacy in either cohort, whereas none of the patients with mutations detectable in plasma responded to therapy. Response rate and disease control rate in plasma KRAS wt patients were 19 and 66% compared with 0 and 37%, in patients with pKRAS mutations, (P=0.04 and 0.01). Tumor KRAS status was not associated with PFS but with OS in the validation cohort. Plasma BRAF and KRAS demonstrated a strong influence on both PFS and OS. The median OS was 13.0 mo in pKRAS wt patients and 7.8 in pKRAS-mutated, (HR=2.26, P<0.0001). PFS was 4.6 and 2.7 mo, respectively (HR=1,69, P=0.01). Multivariate analysis confirmed the independent prognostic value of pKRAS status but not KRAS tumor status.Conclusion:Tumor KRAS has minor clinical impact, whereas plasma KRAS status seems to hold important predictive and prognostic information.

Original languageEnglish
JournalBritish Journal of Cancer
Volume109
Issue number12
Pages (from-to)3067-3072
Number of pages6
ISSN0007-0920
DOIs
Publication statusPublished - 10 Dec 2013
Externally publishedYes

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