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Association details:
Biomarker:KRAS G13
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: B - Late Trials
New
Title:

Cetuximab Plus Irinotecan, Fluorouracil, and Leucovorin As First-Line Treatment for Metastatic Colorectal Cancer: Updated Analysis of Overall Survival According to Tumor KRAS and BRAF Mutation Status

Excerpt:
Mutations in KRAS codon 12 or 13 were detected in the tumor tissue of 397 of 1,063 patients (37%)...Patients in both treatment groups whose tumors carried mutations in KRAS appeared to have worse overall survival than those whose tumors were wild-type (Table 2, Fig 2B). Cox (PFS and overall survival) and logistic regression (best overall response) models were used to explore the relationship in the expanded KRAS population between the magnitude of treatment effect and tumor KRAS mutation status.
Secondary therapy:
FOLFIRI
DOI:
10.1200/JCO.2010.33.5091
Trial ID:
Evidence Level:
Sensitive: C2 – Inclusion Criteria
New
Title:

Randomised Phase II study of cetuximab alone or in combination with irinotecan in patients with metastatic colorectal cancer (CRC) with either KRAS WT or G13D mutation.

Excerpt:
...KRAS G13D ...
Evidence Level:
Sensitive: C2 – Inclusion Criteria
New
Title:

A study to explore the effects of cetuximab alone or in combination with irinotecan in patients with an abnormal gene (KRAS) in their colon cancer cells.

Excerpt:
...Prior confirmation of tumour KRAS status as either KRAS WT (with no mutations or changes in BRAF, NRAS, PIK3CA exon20) OR KRAS G13D mutation,6. ...
Less C2 evidence
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:
When reconsidering response rates according to the mutational status of KRAS, we found that neither regression nor disease stabilization was achieved in any of the 18 cohorts bearing KRAS-mutant (codons 12 and 13) tumors.
DOI:
10.1158/2159-8290.CD-11-0109
Evidence Level:
Resistant: C3 – Early Trials
New
Source:
Title:

Biomarkers of benefit from cetuximab-based therapy in metastatic colorectal cancer: interaction of EGFR ligand expression with RAS/RAF, PIK3CA genotypes

Excerpt:
Specifically, patients with codon 13 mutations reached a median survival of 28 months (95% CI 16–39), those with other rarer KRAS mutations a median survival of 33 months (95% CI 16–42) and patients with KRAS wild-type tumours a median survival of 29 months (95% CI 25–35).
DOI:
10.1186/1471-2407-13-49