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Association details:
| Biomarker: | KRAS G13D |
|---|---|
| Cancer: | Colorectal Cancer |
| Drug: | Erbitux (cetuximab) (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:
KRAS Codon 12 and 13 Mutations in Relation to Disease-Free Survival in BRAF–Wild-Type Stage III Colon Cancers from an Adjuvant Chemotherapy Trial (N0147 Alliance)
Excerpt:
As shown in Fig. 3A and Table 3 (top), patient tumors with KRAS codon 13 mutations experienced shorter DFS (univariate HR, 1.46; 95% CI, 1.13–1.89; P = 0.0035 and multivariate HR, 1.36; 95% CI, 1.04–1.77; P = 0.0248), compared with those that were wild type for KRAS and BRAF, independent of clinicopathologic variables and MMR status.
Secondary therapy:
Modified FOLFOX6
DOI:
10.1158/1078-0432.CCR-13-3140
Source:
Title:
Association of KRAS G13D tumor mutations with outcome in patients with metastatic colorectal cancer treated with first-line chemotherapy with or without cetuximab
Excerpt:
CONTRADICTING EVIDENCE: Within KRAS mutation subgroups, cetuximab plus chemotherapy versus chemotherapy alone significantly improved PFS (median, 7.4 v 6.0 months; hazard ratio [HR], 0.47; P = .039) and tumor response (40.5% v 22.0%; odds ratio, 3.38; P = .042) but not survival (median, 15.4 v 14.7 months; HR, 0.89; P = .68) in patients with G13D-mutant tumors.
Secondary therapy:
FOLFIRI; FOLFOX
DOI:
10.1200/JCO.2012.42.2592
Source:
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 ...
Trial ID:
Source:
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. ...
Trial ID:
Less C2 evidence
Source:
Title:
Association of KRAS p.G13D mutation with outcome in patients with chemotherapy-refractory metastatic colorectal cancer treated with cetuximab
Excerpt:
CONTRADICTING EVIDENCE:...patients with p.G13D-mutated tumors (n = 32) treated with cetuximab had longer overall survival (median, 7.6 [95% confidence interval {CI}, 5.7-20.5] months vs 5.7 [95% CI, 4.9-6.8] months; adjusted hazard ratio [HR], 0.50; 95% CI, 0.31-0.81; P = .005) and longer progression-free survival (median, 4.0 [95% CI, 1.9-6.2] months vs 1.9 [95% CI, 1.8-2.8] months; adjusted HR, 0.51; 95% CI, 0.32-0.81; P = .004).
DOI:
10.1001/jama.2010.1535.
Source:
Title:
Phase II study of single-agent cetuximab in KRAS G13D mutant metastatic colorectal cancer
Excerpt:
...we conducted this hypothesis-confirmatory phase II single-arm trial to provide a prospective proof of the clinical benefit of cetuximab in KRAS G13D mutant mCRC patients...The primary objective of the trial was not met: three patients (25%) were progression-free at 4 months. None of 12 patients achieved response and three patients (25%) had disease stabilisation, for an overall disease control rate (DCR) of 25%. Notably, DCR at 6 months was 0%. Median PFS and OS were 1.9 (95% CI 1.7–3.8) and 7.2 months (95% CI 5.7–9.7), respectively. No unexpected toxicities were observed (grade 3 or 4 skin rash 17%).
DOI:
10.1093/annonc/mdv385
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.
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
