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News

Predictors of a lack of response with panitumumab–FOLFOX4 in colorectal cancer

This week's issue of the New England Journal of Medicine investigates panitumumab–FOLFOX4 treatment and RAS mutations in colorectal cancer.

News image

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."

N Engl J Med 2013; 369:1023-1034
16 September 2013

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