K-ras mutations and benefit from cetuximab in advanced colorectal cancer.

@article{Karapetis2008KrasMA,
  title={K-ras mutations and benefit from cetuximab in advanced colorectal cancer.},
  author={Christos S. Karapetis and Shirin Khambata-Ford and Derek J. Jonker and Christopher J. O'Callaghan and Dongsheng Tu and Niall C Tebbutt and Robert John Simes and Haji Ibraheem Chalchal and Jeremy David Shapiro and Sonia Robitaille and Timothy Jay Price and Lois E. Shepherd and Heather J. Au and Christian Langer and Malcolm J. Moore and John R. Zalcberg},
  journal={The New England journal of medicine},
  year={2008},
  volume={359 17},
  pages={
          1757-65
        }
}
BACKGROUND Treatment with cetuximab, a monoclonal antibody directed against the epidermal growth factor receptor, improves overall and progression-free survival and preserves the quality of life in patients with colorectal cancer that has not responded to chemotherapy. The mutation status of the K-ras gene in the tumor may affect the response to cetuximab and have treatment-independent prognostic value. METHODS We analyzed tumor samples, obtained from 394 of 572 patients (68.9%) with… 

Figures and Tables from this paper

Metastatic colorectal cancer first-line treatment with bevacizumab: the impact of K-ras mutation

The results seem to confirm that K-ras mutation does not have a prognostic role in mCRC patients receiving first-line treatment with bevacizumab.

Involvement of K-RAS mutations and amino acid substitutions in the survival of metastatic colorectal cancer patients

The efficacy of epidermal growth factor-targeting therapies has been found to be limited in tumors with the wild-type K-RAS gene, suggesting a predictive value of K- RAS gene analysis in tumoral response, but further research is needed in patients treated in prospective controlled trials.

Prognostic significance of K-Ras mutation rate in metastatic colorectal cancer patients

The data demonstrate an association between K-Ras mutation rate and prognosis in mCRC patients treated with bevacizumab-containing first-line therapy, and a multivariate model adjusted for age at diagnosis, site of origin of tumor tissue, referral center, number of metastatic sites, and first- line chemotherapy backbone showed that K-CRC mutation rate remained a significant predictor of PFS and OS in the whole population.

TP53 mutations predict disease control in metastatic colorectal cancer treated with cetuximab-based chemotherapy

TP53 mutations are predictive of cetuximab sensitivity, particularly in patients without KRAS mutation, and that TP53 genotyping could have a clinical interest to select patients who should benefit from cetUXimab-based CT.

Clinical impact of K-ras mutation in colorectal cancer patients treated with adjuvant FOLFOX

It was shown that K-ras status was not associated with clinical outcome in patients treated with adjuvant FOLFOX, and with the exception of tumor location in DFS and OS, no differences in other variables were observed.

Evaluating the treatment of metastatic colorectal cancer with monoclonal antibodies

A large number of trials evaluated the K-RAS status and the first-line treatment of metastatic colorectal cancer, the treatment of refractory metastatic cancer and dual-antibody therapy in the first line treatment of coloreCTal cancer.

Analysis of the role of RAS Family Mutations in Metastatic Colorectal Cancer (mCRC): Current Treatment Practice

Even if patients’ outcome under anti-EGFR moAbs therapy is improved with better selection based on Ras mutational status, more research is needed in this field; the matter is far from being resolved, since there are still a minority of wt RAS patients who do not respond upfront to such a treatment.

EGFR L2 domain mutation is not correlated with resistance to cetuximab in metastatic colorectal cancer patients

The findings do not provide sufficient evidence that EGFR L2 domain mutation is correlated with resistance to cetuximab, but one patient who had a mutation at exon 9 showed a partial response to cETuxIMab plus irinotecan.

The Effect of EGFR Inhibitor Treatment in KRAS G13D Mutated Metastatic Colorectal Cancer Background

The investigation of EGFR-I in KRAS G13D mutated metastatic CRC is a good example of the ability of international collaboration to perform RCTs even in rare molecular subtypes, as well as confirming the role of prospective clinical trial evaluation of hypotheses raised by unplanned subgroup analyses.
...

References

SHOWING 1-10 OF 32 REFERENCES

KRAS mutation status is predictive of response to cetuximab therapy in colorectal cancer.

KRAS mutations are a predictor of resistance to cetuximab therapy and are associated with a worse prognosis, and the EGFR amplification, which is not as frequent as initially reported, is also associated with response to this treatment.

KRAS mutations as an independent prognostic factor in patients with advanced colorectal cancer treated with cetuximab.

These results confirm the high prognostic value of KRAS mutations on response to cetuximab and survival in metastatic CRC patients treated with cetUXimab.

Cetuximab for the treatment of colorectal cancer.

Cetuximab improves overall survival and progression-free survival and preserves quality-of-life measures in patients with colorectal cancer in whom other treatments have failed.

Expression of epiregulin and amphiregulin and K-ras mutation status predict disease control in metastatic colorectal cancer patients treated with cetuximab.

Gene expression profiles showed that patients with tumors that express high levels of the EGFR ligands epiregulin and amphireGulin and patients with wild-type K-ras are more likely to have disease control on cetuximab treatment.

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

It is confirmed that KRAS mutation is highly predictive of a non-response to cetuximab plus chemotherapy in MCRC and highlights the need to use sensitive molecular methods, such as SNaPshot or PCR-LCR assays, to ensure an efficient mutation detection.

EGFR and KRAS mutations as criteria for treatment with tyrosine kinase inhibitors: retro- and prospective observations in non-small-cell lung cancer.

Results of individualized therapy guided by mutational tumor profile of patients with non-small-cell lung cancer are presented and confirm the potential role of EGFR and KRAS mutations in predicting (non)response to TKIs.

K-ras and p16 aberrations confer poor prognosis in human colorectal cancer.

Results suggest that the combined K-ras and p16 analyses may be of prognostic use in human colorectal cancer.

KRAS Mutation Is an Important Predictor of Resistance to Therapy with Epidermal Growth Factor Receptor Tyrosine Kinase Inhibitors in Non–Small-Cell Lung Cancer

KRAS mutation should be included as indicator of resistance in the panel of markers used to predict response to EGFR-TKIs in NSCLC.

Cyclin D1 and epidermal growth factor polymorphisms associated with survival in patients with advanced colorectal cancer treated with Cetuximab

The findings of this pilot study suggest that the cyclin D1 A870G and the EGF A61G polymorphisms may be useful molecular markers for predicting clinical outcome in CRC patients treated with single-agent Cetuximab.