Patients with metastatic colorectal cancer (CRC) who have KRAS –mutated tumors are currently excluded from treatment with the antiepidermal growth factor monoclonal antibodies cetuximab and panitumumab. A new study, however, suggests that patients with a KRAS codon 13 mutation have better outcomes when treated with cetuximab than patients with other KRAS mutations.
This study, the authors say, is the first to demonstrate a positive association between KRAS p.G13D mutations and cetuximab treatment in regard to survival. The results are reported in the October 27 issue of JAMA.
In a retrospective, observational study, Wendy De Roock, MD, of the University of Leuven, Belgium, and associates analyzed the association between KRAS mutation status (p.G13D vs other KRAS mutations) in 579 patients with chemotherapy-refractory CRC who were treated with cetuximab between 2001 and 2008.
They found that compared with patients with other KRAS mutations, those with p.G13D-mutated tumors had significantly longer overall survival (median, 7.6 months vs 5.7 months) and progression-free survival (median, 4.0 months vs 1.9 months). There was a significant association between KRAS mutation status and overall survival benefit with cetuximab treatment.
In vitro analysis showed that like KRAS wild-type cells, p.G13D-mutated colorectal cells were sensitive to cetuximab but p.G12V-mutated cells were not.
The results suggest that prospective randomized trials of cetuximab in patients with metastic CRC who have a p.G13D mutation may be warranted, the authors conclude.