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Association details:
Biomarker:KRAS Q61
Cancer:Colorectal Cancer
Drug:Erbitux (cetuximab) (EGFR inhibitor)
Direction:Resistant
Evidence:
Evidence Level:
Resistant: A1 - Approval
New
Source:
Excerpt:
ERBITUX is not indicated for the treatment of patients with CRC that harbor somatic mutations in exon 2 (codons 12 and 13), exon 3 (codons 59 and 61), and exon 4 (codons 117 and 146) of either K-Ras or N-Ras and hereafter is referred to as “Ras” or when the Ras status is unknown.
Evidence Level:
Resistant: C3 – Early Trials
New
Title:

KRAS codon 61, 146 and BRAF mutations predict resistance to cetuximab plus irinotecan in KRAS codon 12 and 13 wild-type metastatic colorectal cancer

Excerpt:
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.
Secondary therapy:
irinotecan
DOI:
10.1038/sj.bjc.6605177
Evidence Level:
Resistant: C3 – Early Trials
New
Title:

A Molecularly Annotated Platform of Patient-Derived Xenografts (“Xenopatients”) Identifies HER2 as an Effective Therapeutic Target in Cetuximab-Resistant Colorectal Cancer

Excerpt:
Because our KRAS (codons 12 and 13) wild-type subpopulation included all these genotypes and additional KRAS rare mutations at codons 61 and 146, we decided to exploit our platform to challenge the predictive value of these emerging biomarkers. Our results prospectively validated observations in patients: none of the 7 NRAS- and 3 BRAF-mutant cases (10.6% and 4.5%, respectively) or the 4 cases with KRAS rare mutations (6.1%) responded to cetuximab with tumor shrinkage or stabilization.
DOI:
10.1158/2159-8290.CD-11-0109