Panitumumab-FOLFOX4 treatment and RAS mutations in colorectal cancer.

@article{Douillard2013PanitumumabFOLFOX4TA,
  title={Panitumumab-FOLFOX4 treatment and RAS mutations in colorectal cancer.},
  author={Jean-Yves Douillard and Kelly S. Oliner and Salvatore Siena and Josep M. Tabernero and Ronald Burkes and Mario Edmundo Barugel and Yves Humblet and Gy{\"o}rgy Bodoky and David Cunningham and Jacek Jassem and Fernando Rivera and Ilona Koc{\'a}kov{\'a} and Paul Ruff and Maria Błasińska-Morawiec and Martin {\vS}makal and Jean Luc Canon and Mark Rother and Richard Thomas Williams and Alan Rong and Jeffrey S. Wiezorek and Roger Sidhu and Scott Patterson},
  journal={The New England journal of medicine},
  year={2013},
  volume={369 11},
  pages={
          1023-34
        }
}
BACKGROUND Patients with metastatic colorectal cancer that harbors KRAS mutations in exon 2 do not benefit from anti-epidermal growth factor receptor (EGFR) therapy. Other activating RAS mutations may also be negative predictive biomarkers for anti-EGFR therapy. METHODS In this prospective-retrospective analysis, we assessed the efficacy and safety of panitumumab plus oxaliplatin, fluorouracil, and leucovorin (FOLFOX4) as compared with FOLFOX4 alone, according to RAS (KRAS or NRAS) or BRAF… 

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...

References

SHOWING 1-10 OF 33 REFERENCES

Wild-type BRAF is required for response to panitumumab or cetuximab in metastatic colorectal cancer.

BRAF wild-type is required for response to panitumumab or cetuximab and could be used to select patients who are eligible for the treatment and should be used for selection.

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.

The addition of cetuximab to FOLFIRI as first-line treatment for metastatic colorectal cancer (mCRC) was shown to reduce the risk of disease progression and increase the chance of response in patients with KRAS wild-type disease.

Panitumumab combined with irinotecan for patients with KRAS wild-type metastatic colorectal cancer refractory to standard chemotherapy: a GERCOR efficacy, tolerance, and translational molecular study.

Panitumumab and irinotecan is an active third-line regimen in a well-defined population based on biomarkers in patients with KRAS wild-type metastatic colorectal cancer refractory to standard chemotherapy.

Efficacy according to biomarker status of cetuximab plus FOLFOX-4 as first-line treatment for metastatic colorectal cancer: the OPUS study.

These results confirm the efficacy of cetuximab plus FOLFOX-4 in the first-line treatment of patients with KRAS wild-type mCRC and confirm KRAS mutation status as an effective predictive biomarker.

Association of KRAS p.G13D mutation with outcome in patients with chemotherapy-refractory metastatic colorectal cancer treated with cetuximab.

Use of cetuximab was associated with longer overall and progression-free survival among patients with chemotherapy-refractory colorectal cancer with p.G13D-mutated tumors than with other KRAS-mutation tumors.

Mutant KRAS codon 12 and 13 alleles in patients with metastatic colorectal cancer: assessment as prognostic and predictive biomarkers of response to panitumumab.

Results across three treatment regimens suggest that patients with mutant KRAS codon 12 or 13 mCRC tumors are unlikely to benefit from panitumumab therapy.

Randomized phase III study of panitumumab with fluorouracil, leucovorin, and irinotecan (FOLFIRI) compared with FOLFIRI alone as second-line treatment in patients with metastatic colorectal cancer.

  • M. PeetersT. Price J. Gansert
  • Medicine, Biology
    Journal of clinical oncology : official journal of the American Society of Clinical Oncology
  • 2010
Panitumumab plus FOLFIRI significantly improved PFS and is well-tolerated as second-line treatment in patients with WT KRAS mCRC.

Frequency of KRAS, BRAF, and NRAS mutations in colorectal cancer

While further study is needed to determine the full therapeutic implications of mutations in these codons, mutational testing of thesecodons may be useful for identifying a significant proportion of patients who may also be resistant to anti‐EGFR therapies.

KRAS codon 61, 146 and BRAF mutations predict resistance to cetuximab plus irinotecan in KRAS codon 12 and 13 wild-type metastatic colorectal cancer

Assessing KRAS codons 61/146 and BRAF V600E mutations might help optimising the selection of the candidate patients to receive anti-EGFR moAbs in metastatic colorectal cancer.