Fluorouracil, Leucovorin, and Irinotecan Plus Cetuximab Treatment and RAS Mutations in Colorectal Cancer

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.