KRAS status analysis and anti-EGFR therapies: is comprehensiveness a biologist's fancy or a clinical necessity?
| Autor: | Mineur L, Lamy Pj, Evelyne Lopez-Crapez, Emptas H |
|---|---|
| Rok vydání: | 2010 |
| Předmět: |
Adult
Proto-Oncogene Proteins B-raf Male Cancer Research endocrine system diseases DNA Mutational Analysis Antineoplastic Agents colorectal cancer Kaplan-Meier Estimate Biology Adenocarcinoma Bioinformatics medicine.disease_cause Antibodies Monoclonal Humanized Irinotecan Disease-Free Survival BRAF Proto-Oncogene Proteins p21(ras) Biologist Proto-Oncogene Proteins Antineoplastic Combined Chemotherapy Protocols cetuximab medicine Biomarkers Tumor KRAS Humans Neoplasm Metastasis Letters to the Editor Codon neoplasms Aged Carcinoma Antibodies Monoclonal Genetics and Genomics Middle Aged digestive system diseases respiratory tract diseases ErbB Receptors Genes ras Oncology Drug Resistance Neoplasm Mutation ras Proteins Camptothecin Female Colorectal Neoplasms Medical Futility |
| Zdroj: | British Journal of Cancer |
| ISSN: | 1532-1827 |
| Popis: | Background: KRAS codons 12 and 13 mutations predict resistance to anti-EGFR monoclonal antibodies (moAbs) in metastatic colorectal cancer. Also, BRAF V600E mutation has been associated with resistance. Additional KRAS mutations are described in CRC. Methods: We investigated the role of KRAS codons 61 and 146 and BRAF V600E mutations in predicting resistance to cetuximab plus irinotecan in a cohort of KRAS codons 12 and 13 wild-type patients. Results: Among 87 KRAS codons 12 and 13 wild-type patients, KRAS codons 61 and 146 were mutated in 7 and 1 case, respectively. None of mutated patients responded vs 22 of 68 wild type (P=0.096). Eleven patients were not evaluable. KRAS mutations were associated with shorter progression-free survival (PFS, HR: 0.46, P=0.028). None of 13 BRAF-mutated patients responded vs 24 of 74 BRAF wild type (P=0.016). BRAF mutation was associated with a trend towards shorter PFS (HR: 0.59, P=0.073). In the subgroup of BRAF wild-type patients, KRAS codons 61/146 mutations determined a lower response rate (0 vs 37%, P=0.047) and worse PFS (HR: 0.45, P=0.023). Patients bearing KRAS or BRAF mutations had poorer response rate (0 vs 37%, P=0.0005) and PFS (HR: 0.51, P=0.006) compared with KRAS and BRAF wild-type patients. Conclusion: Assessing KRAS codons 61/146 and BRAF V600E mutations might help optimising the selection of the candidate patients to receive anti-EGFR moAbs. |
| Databáze: | OpenAIRE |
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