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|Ref Type||Journal Article|
|Authors||Van Cutsem E, Lenz HJ, Köhne CH, Heinemann V, Tejpar S, Melezínek I, Beier F, Stroh C, Rougier P, van Krieken JH, Ciardiello F|
|Title||Fluorouracil, leucovorin, and irinotecan plus cetuximab treatment and RAS mutations in colorectal cancer.|
|Journal||Journal of clinical oncology : official journal of the American Society of Clinical Oncology|
|Date||2015 Mar 01|
|Abstract Text||The phase III CRYSTAL study demonstrated that addition of cetuximab to fluorouracil, leucovorin, and irinotecan (FOLFIRI) significantly improved overall survival, progression-free survival, and objective response in the first-line treatment of patients with KRAS codon 12/13 (exon 2) wild-type metastatic colorectal cancer (mCRC). Outcome was reassessed in subgroups defined by extended RAS mutation testing.Existing DNA samples from KRAS exon 2 wild-type tumors from CRYSTAL study patients were reanalyzed for other RAS mutations in four additional KRAS codons (exons 3 and 4) and six NRAS codons (exons 2, 3, and 4) using beads, emulsion, amplification, and magnetics technology. No tissue microdissection was performed. A ≥ 5% mutant allele cutoff was used to call mutations.Mutation status was evaluable in 430 (64.6%) of 666 patients with KRAS exon 2 wild-type tumors. Other RAS mutations were detected in 63 (14.7%) of 430 patients. In those with RAS wild-type tumors, a significant benefit across all efficacy end points was associated with the addition of cetuximab to FOLFIRI. In patients with other RAS tumor mutations, no difference in efficacy outcomes between treatment groups was seen. The safety profile in RAS subgroups was similar and in line with expectations.In the first-line treatment of mCRC, patients with RAS wild-type tumors derived a significant benefit from the addition of cetuximab to FOLFIRI; patients with RAS tumor mutations did not. Molecular testing of tumors for all activating RAS mutations is essential before considering anti-epidermal growth factor receptor therapy, thereby allowing the further tailoring of cetuximab administration to maximize patient benefit.|
|Molecular Profile||Treatment Approach|
|Gene Name||Source||Synonyms||Protein Domains||Gene Description||Gene Role|
|Therapy Name||Drugs||Efficacy Evidence||Clinical Trials|
|Drug Name||Trade Name||Synonyms||Drug Classes||Drug Description|
|Gene||Variant||Impact||Protein Effect||Variant Description||Associated with drug Resistance|
|Molecular Profile||Indication/Tumor Type||Response Type||Therapy Name||Approval Status||Evidence Type||Efficacy Evidence||References|
|NRAS wild-type||colorectal cancer||predicted - sensitive||Cetuximab + Fluorouracil + Irinotecan + Leucovorin||Phase III||Actionable||In a Phase III trial, the combination of Erbitux (cetuximab) and FOLFIRI demonstrated a significant clinical benefit in OS, PFS, and objective response compared to FOLFIRI alone in colorectal cancer patients with RAS wild-type status (PMID: 25605843).||25605843|
|NRAS mutant||colorectal cancer||no benefit||Cetuximab + Fluorouracil + Irinotecan + Leucovorin||Phase III||Actionable||In a retrospective analysis of a Phase III trial, the combination of Erbitux (cetuximab) and FOLFIRI did not demonstrate an improved clinical benefit compared to FOLFIRI alone in colorectal cancer patients with RAS mutations (PMID: 25605843).||25605843|