Annotation Detail
Information
- Associated Genes
- KRAS
- Associated Variants
-
KRAS G12/G13
KRAS G12/G13 - Associated Disease
- colorectal cancer
- Source Database
- CIViC Evidence
- Description
- This was a retrospective clinical study of 92 metastatic colorectal cancer patients who received cetuximab in conjunction with salvage chemotherapy (refractory to at least one line of treatment). Salvage chemotherapy was composed of 5-fluorouracil (5-FU) only, 5-FU + oxaliplatin, 5-FU + irinotecan, or 5-FU + oxaliplatin + irinotecan. The study assessed the relationship between KRAS mutation status in primary tumors and response to cetuximab-containing salvage chemotherapy, as measured by PFS. Of the 92 patients, 60 had wildtype KRAS and 32 had mutations in KRAS—including G12A, G12C, G12D, G12R, G12S, G12V, and G13D. The study found that patients harboring a KRAS mutation were trending toward resistance to cetuximab-containing salvage chemotherapy as compared to patients with wildtype KRAS (p=0.094). Note: while differences in PFS were nonsignificant between patients with wildtype or mutant KRAS, differences in objective response (defined as reduction by at least 30% in the sum of the longest diameters of target lesions compared to baseline) were significantly different. Of the 32 patients with mutant KRAS, none responded to cetuximab-containing salvage therapy, while 14/60 of the patients with wildtype KRAS (23%) responded (p=.002).
- Variant Origin
- somatic
- Variant Origin
- Somatic
- Evidence URL
- https://civic.genome.wustl.edu/links/evidence_items/6296
- Gene URL
- https://civic.genome.wustl.edu/links/genes/30
- Variant URL
- https://civic.genome.wustl.edu/links/variants/77
- Rating
- 3
- Evidence Type
- Predictive
- Disease
- Colorectal Cancer
- Evidence Direction
- Supports
- Drug
- Cetuximab
- Evidence Level
- B
- Clinical Significance
- Resistance
- Pubmed
- 19603024
Drugs
| Drug Name | Sensitivity | Supported |
|---|---|---|
| Cetuximab | Resitance or Non-Reponse | true |