KRAS Codon 12 and 13 Mutations in Relation to Disease-Free Survival in BRAF–Wild-Type Stage III Colon Cancers from an Adjuvant Chemotherapy Trial (N0147 Alliance)

Autor: Qian Shi, Suresh G. Nair Md, Garth D. Nelson, David Tougeron, Frank A. Sinicrope, Steven R. Alberts, Michelle R. Mahoney, Richard M. Goldberg, Stephen N. Thibodeau, Daniel J. Sargent, Harry H. Yoon
Rok vydání: 2014
Předmět:
Male
Oncology
Cancer Research
Organoplatinum Compounds
endocrine system diseases
DNA Mutational Analysis
Leucovorin
Cetuximab
Kaplan-Meier Estimate
medicine.disease_cause
FOLFOX
Antineoplastic Combined Chemotherapy Protocols
Aged
80 and over

Mutation
Middle Aged
Chemotherapy
Adjuvant

Colonic Neoplasms
Female
DNA mismatch repair
Fluorouracil
KRAS
medicine.drug
Adult
Proto-Oncogene Proteins B-raf
medicine.medical_specialty
Adenocarcinoma
Antibodies
Monoclonal
Humanized

Malignancy
Disease-Free Survival
Article
Proto-Oncogene Proteins p21(ras)
Young Adult
Proto-Oncogene Proteins
Internal medicine
medicine
Humans
Codon
neoplasms
Aged
Neoplasm Staging
Proportional Hazards Models
business.industry
Proportional hazards model
Cancer
medicine.disease
digestive system diseases
Immunology
ras Proteins
business
Multiplex Polymerase Chain Reaction
Zdroj: Clinical Cancer Research. 20:3033-3043
ISSN: 1557-3265
1078-0432
Popis: Purpose: We examined the prognostic impact of specific KRAS mutations in patients with stage III colon adenocarcinoma receiving adjuvant FOLFOX alone or combined with cetuximab in a phase III trial (N0147). Analysis was restricted to BRAF–wild-type tumors, because BRAF mutation was associated with poor prognosis, and BRAF and KRAS mutations are mutually exclusive. Experimental Design: The seven most common KRAS mutations in codon 12 and codon 13 were examined in 2,478 BRAF–wild-type tumors. Because KRAS mutations in codon 12 (n = 779) or 13 (n = 220) were not predictive of adjuvant cetuximab benefit, study arms were pooled for analysis. Disease-free survival (DFS) was evaluated by HRs using Cox models. Results: KRAS mutations in codon 12 (multivariate HR, 1.52; 95% confidence interval, CI, 1.28–1.80; P < 0.0001) or codon 13 (multivariate HR, 1.36; 95% CI, 1.04–1.77; P = 0.0248) were significantly associated with shorter DFS compared with patients with wild-type KRAS/BRAF tumors, independent of covariates. KRAS codon 12 mutations were independently associated with proficient mismatch repair (P < 0.0001), proximal tumor site (P < 0.0001), low grade, age, and sex, whereas codon 13 mutations were associated with proximal site (P < 0.0001). Conclusion: KRAS mutations in either codon 12 or 13 are associated with inferior survival in patients with resected stage III colon cancer. These data highlight the importance of accurate molecular characterization and the significant role of KRAS mutations in both codons in the progression of this malignancy in the adjuvant setting. Clin Cancer Res; 20(11); 3033–43. ©2014 AACR.
Databáze: OpenAIRE