Patients with metastatic colorectal cancer that harbor KRAS mutations in exon 2 do not benefit from anti–epidermal growth factor receptor therapy.
Other activating RAS mutations may also be negative predictive biomarkers for anti-epidermal growth factor receptor therapy.
In this prospective–retrospective analysis, Dr Jean-Yves Douillard and colleagues assessed the efficacy and safety of panitumumab plus oxaliplatin, fluorouracil, and leucovorin (FOLFOX4) as compared with FOLFOX4 alone, according to RAS or BRAF mutation status.
|Overall survival was 26 months in the panitumumab–FOLFOX4 group|
|New England Journal of Medicine|
The research team analyzed a total of 639 patients who had metastatic colorectal cancer without KRAS mutations in exon 2.
The patients had results for at least one of the following: KRAS exon 3 or 4; NRAS exon 2, 3, or 4; or BRAF exon 15.
The overall rate of ascertainment of RAS status was 90%.
Among 512 patients without RAS mutations, progression-free survival was 10 months with panitumumab–FOLFOX4 versus 8 months with FOLFOX4 alone.
The team observed that overall survival was 26 months in the panitumumab–FOLFOX4 group versus 20 months in the FOLFOX4-alone group.
The doctors also found that a total of 108 patients with nonmutated KRAS exon 2 had other RAS mutations.
These mutations were associated with inferior progression-free survival and overall survival with panitumumab–FOLFOX4 treatment, which was consistent with the findings in patients with KRAS mutations in exon 2.
BRAF mutations were a negative prognostic factor.
No new safety signals were identified.
Dr Douillard's team concludes, "Additional RAS mutations predicted a lack of response in patients who received panitumumab–FOLFOX4."
"In patients who had metastatic colorectal cancer without RAS mutations, improvements in overall survival were observed with panitumumab–FOLFOX4 therapy."