Heinz-Josef Lenz, MD, from the USC Norris Comprehensive Cancer Center, discusses the potential predictive impact of KRAS and NRAS mutations in metastatic colorectal cancer.
Heinz-Josef Lenz, MD, the co-director of the Colorectal Center and GI Oncology Program at the USC Norris Comprehensive Cancer Center, discusses the potential predictive impact of traditionally wild-type KRAS and NRAS mutations in metastatic colorectal cancer (mCRC).
To date, Lenz notes, KRAS testing has been restricted to codons 12 and 13; however, the phase II PEAK trial suggests that testing should now include codons 61, 117, and 146. This trial examined the affects of non-traditional (wild-type) activating KRAS and NRAS mutations on the clinical activity of EGFR inhibitors. Overall, Lenz suggests, testing for these additional codons could help screen 20% more patients with mCRC for treatment with EGFR inhibitors.
PEAK is a phase II trial and these data have not yet been validated, Lenz points out. As such, analyses will be applied to the FIRE-3 and the CALGB 8045 trials to see if these findings can be further validated. If they can, this could have a dramatic impact on how patients with mCRC are screened and treated, Lenz believes. This method could help to more accurately select patients who will benefit from EGFR inhibitors.