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Medline ® Abstract for Reference 37

of 'Systemic chemotherapy for nonoperable metastatic colorectal cancer: Treatment recommendations'

Influence of KRAS p.G13D mutation in patients with metastatic colorectal cancer treated with cetuximab.
Gajate P, Sastre J, Bando I, Alonso T, Cillero L, Sanz J, Caldés T, Díaz-Rubio E
Clin Colorectal Cancer. 2012;11(4):291. Epub 2012 Apr 25.
BACKGROUND: Patients with metastatic colorectal cancer (mCRC) with activating mutations at codon 12 or 13 of the KRAS gene are currently excluded from treatment with monoclonal antibodies against the epidermal growth factor receptor (EGFR), for example, cetuximab. Occasionally, some of these patients benefit from treatment with cetuximab, especially patients with a mutation at codon 13. We conducted an analysis to study the influence of the KRAS p.G13D mutation in patients with mCRC who were treated with cetuximab.
MATERIALS AND METHODS: We analyzed the KRAS mutation status of 110 patients who were treated with cetuximab between September 2003 and October 2008 at Hospital Clínico, San Carlos. We compared progression-free survival, overall survival, and response rate according to KRAS mutation status.
RESULTS: Patients with mutations at codon 13 compared with those with other KRAS mutations showed no statistically significant differences in progression-free survival (4.96 months [95% CI, 3.04-6.89 months]vs. 3.10 months [95% CI, 1.58-4.61 months]; hazard ratio [HR]0.88 [95% CI, 44-1.75]; P = .72) and overall survival (8.2 months [95% CI, 4.2-12.1 months]vs. 14.6 months [95% CI, 8.0-21.2 months]; HR 0.50 [95% CI, 0.23-1.09]; P = .084). Patients with KRAS wild-type tumors have a longer progression-free survival (7.30 months [95% CI, 4.48-10.12 months]; HR 0.46 [95% CI, 0.23-0.91]; P = .025) and overall survival (19.0 months [95% CI, 10.2-27.8 months]; HR 0.32 [95% CI, 0.15-0.69]; P = .004) than patients with p.G13D-mutated tumors. Differences in the response rate were not observed between groups.
CONCLUSION: Patients with mCRC and mutation at codon 13 of the KRAS gene do not appear to benefit from treatment with cetuximab. These results support the current clinical practice.
Department of Clinical Oncology, Hospital Clínico San Carlos (HCSC), Madrid, Spain. pgajate.hcsc@gmail.com