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Association details:
Biomarker:KRAS G12
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.
DOI:
10.1200/JCO.2010.33.5091
Trial ID:
Evidence Level:
Sensitive: C2 – Inclusion Criteria
New
Title:

Study of JDQ443 , in combination with trametinib or ribociclib or cetuximab, in advanced cancer with a specific mutation (changes in a gene) called KRAS G12C

Excerpt:
...Dose Escalation:•Patients with advanced (metastatic or unresectable) KRAS G12C mutant solid tumors who have received standard of care therapy or are ineligible to receive such therapy.Phase II:•Patients with advanced (metastatic or unresectable) KRAS G12C mutant non-small cell lung cancer who have received platinum-based chemotherapy regimen and immune checkpoint inhibitor therapy, unless patient was ineligible to receive such therapy•Patients with advanced (metastatic or unresectable) KRAS G12C mutant colorectal cancer who have received fluropyrimidine-, oxaliplatin-, and irinotecan-based chemotherapy, unless patient was ineligible to such therapy.All patients:•ECOG performance status of 0 or 1.•Patients must have a site of disease amenable to biopsy and be a candidate for tumor biopsy according to the treating institution's guidelines.`...
Evidence Level:
Resistant: C3 – Early Trials
New
Title:

Clinical relevance of KRAS mutation detection in metastatic colorectal cancer treated by Cetuximab plus chemotherapy

Excerpt:
Remarkably, no KRAS mutation was found in the 12 patients with clinical response. KRAS mutation was associated with disease progression (P=0.0005) and TTP was significantly decreased in mutated KRAS patients (3 vs 5.5 months, P=0.015).
Secondary therapy:
oxaliplatin; irinotecan
DOI:
10.1038/sj.bjc.6603685
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:
Further subgroup analyses showed that the median survival in patients with codon 12 KRAS mutations was also lower than the median survival of all other patient subgroups (other KRAS mutations or KRAS wild-type).
DOI:
10.1186/1471-2407-13-49
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