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Association details:
| Biomarker: | KRAS G13D |
|---|---|
| Cancer: | Colorectal Cancer |
| Drug: | Vectibix (panitumumab) (EGFR inhibitor) |
| Direction: | Resistant |
Evidence:
Source:
Excerpt:
The panel believes that patients with any known KRAS mutation, including G13D, should not be treated with cetuximab or panitumumab.
Source:
Title:
PD-0025 Evaluation of Codon 12 and 13 KRAS Mutations as Biomarkers of Response to Panitumumab in Patients with Metastatic Colorectal Cancer
Excerpt:
Only two individual MT KRAS alleles were significantly associated with outcomes by interaction testing: in the panitumumab + FOLFOX4 arm of study 20050203 G12V was favorably and G13D was unfavorably associated with OS....The results from this retrospective analysis of three phase 3 trials indicate that patients with MT KRAS codon 12 or 13 mCRC tumors are unlikely to benefit from panitumumab therapy.
Secondary therapy:
FOLFOX4
DOI:
10.1016/S0923-7534(20)30001-6
Trial ID:
Source:
Title:
Wild-Type KRAS Is Required for Panitumumab Efficacy in Patients With Metastatic Colorectal Cancer
Excerpt:
The treatment effect on PFS in the wild-type (WT) KRAS group (hazard ratio [HR], 0.45; 95% CI: 0.34 to 0.59) was significantly greater (P < .0001) than in the mutant group (HR, 0.99; 95% CI, 0.73 to 1.36). Median PFS in the WT KRAS group was 12.3 weeks for panitumumab and 7.3 weeks for BSC. Response rates to panitumumab were 17% and 0%, for the WT and mutant groups, respectively. WT KRAS patients had longer overall survival (HR, 0.67; 95% CI, 0.55 to 0.82; treatment arms combined)....Table 2. Distribution of KRAS Mutations By Treatment Arm.
DOI:
10.1200/JCO.2007.14.7116
Source:
Title:
AMPK activation overcomes anti-EGFR antibody resistance induced by KRAS mutation in colorectal cancer
Published date:
07/23/2020
Excerpt:
...DLD1 cells with WT (+/−) or KRAS G13D mutant allele were treated with different concentrations of Cet or Pab... In contrast, DLD1 cells with mutated KRAS showed resistance to Cet and Pab treatment...HCT-116, T84, LoVo (all KRAS G13D mutants), and SW480 (KRAS G12V mutant). The cell lines with KRAS mutations were less sensitive to Cet-induced death and had higher IC50 values...
DOI:
10.1186/s12964-020-00584-z
Source:
Title:
KRAS G13D Mutation and Sensitivity to Cetuximab or Panitumumab in a Colorectal Cancer Cell Line Model
Excerpt:
Contradicting evidence: After treatment with cetuximab or panitumumab, at the optimum concentration of 8 μg/well, the KRAS G13D mutant cell lines HCT-116, LoVo, and T84 showed intermediate sensitivity to both treatments, between the resistant KRAS G12V mutant cell line SW480 and the sensitive KRAS wild-type cell line LIM1215. One of the G13D cell lines was significantly more sensitive to panitumumab than to cetuximab (P = .02).
Source:
Title:
KRAS p.G13D mutations are associated with sensitivity to anti-EGFR antibody treatment in colorectal cancer cell lines
Excerpt:
Contradicting Evidence: Four out of seven KRAS-mutated cell lines were characterised by the p.G13D mutation. Treatment of these cells using Cmab/Pmab induced a significant growth inhibition in contrast to cell lines showing a KRAS mutation at codon 12 or 61.
DOI:
10.1007/s00432-012-1319-7
