The importance of KRAS mutations and EGF61A>G polymorphism to the effect of cetuximab and irinotecan in metastatic colorectal cancer

Autor: Niels Pallisgaard, Jan Lindebjerg, A. A. Rasmussen, K. L. Garm Spindler, Rikke Fredslund Andersen, Dorthe G. Crüger, Anders Jakobsen
Předmět:
Male
Oncology
Time Factors
Colorectal cancer
DNA Mutational Analysis
Cetuximab
Kaplan-Meier Estimate
medicine.disease_cause
Metastasis
Antineoplastic Combined Chemotherapy Protocols
Epidermal growth factor receptor
Neoplasm Metastasis
biology
Antibodies
Monoclonal
Hematology
Middle Aged
ErbB Receptors
Gene Expression Regulation
Neoplastic
Treatment Outcome
Female
KRAS
Colorectal Neoplasms
medicine.drug
Adult
medicine.medical_specialty
Single-nucleotide polymorphism
Antibodies
Monoclonal
Humanized
Irinotecan
Polymorphism
Single Nucleotide
Risk Assessment
Disease-Free Survival
Proto-Oncogene Proteins p21(ras)
Proto-Oncogene Proteins
Internal medicine
Biomarkers
Tumor
medicine
Humans
Aged
Proportional Hazards Models
Retrospective Studies
Epidermal Growth Factor
business.industry
Patient Selection
Cancer
medicine.disease
digestive system diseases
Mutation
Immunology
ras Proteins
biology.protein
Camptothecin
business
Zdroj: Europe PubMed Central
Spindler, K-L G, Pallisgaard, N, Rasmussen, A A, Lindebjerg, J, Andersen, R F, Crüger, D & Jakobsen, A 2009, ' The importance of KRAS mutations and EGF61A >G polymorphism to the effect of cetuximab and irinotecan in metastatic colorectal cancer ', Annals of Oncology, vol. 20, no. 5, pp. 879-884 . https://doi.org/10.1093/annonc/mdn712
DOI: 10.1093/annonc/mdn712
Popis: Udgivelsesdato: 2009-Jan-29 BACKGROUND: The effect of anti-epidermal growth factor receptor (EGFR) antibodies (mAb) in metastatic colorectal cancer seems limited to KRAS wild-type (wt) tumours, but still a major fraction of KRASwt patients are nonresponders and supplementary selection criteria are needed. We investigated methodological aspects of KRAS testing and the predictive and prognostic value of KRAS status combined with three EGFR-related gene polymorphisms [single-nucleotide polymorphisms (SNPs)] in patients treated with cetuximab and irinotecan. PATIENTS AND METHODS: The study included 71 patients referred to third-line cetuximab-irinotecan. Blood samples were analysed for SNPs. KRAS analysis was carried out by sequencing analysis and quantitative PCR (DxS kit) in primary tumour and distant metastases. RESULTS: There was a clear correlation between KRAS status in primary tumours and metastasis. The DxS kit presented the highest sensitivity. Response was confined to KRASwt patients (40% response rate versus 0%, P < 0.1(-3)), which translated into a significant difference in PFS. The EGF61A>G polymorphism showed relation to clinical outcome. A combined biomarker analysis showed a 19% progression rate in KRASwt-EGF61 homozygote patients and 60% in the EGF61A/G patients (P = 0.006) and a significant increase in overall survival (17.1 versus 5.9 months, log-rank, P = 0.002). CONCLUSION: The combined biomarker analysis maybe an attractive approach to selection of patients for third-line treatment including anti-EGFR mAbs.
Databáze: OpenAIRE
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