NEW YORK (Reuters Health) For patients with epidermal growth factor (EGF) receptor-positive colorectal cancer and unresectable metastases, adding cetuximab to first-line treatment with irinotecan, fluorouracil, and leucovorin (FOLFIRI) can reduce the risk of progression if the tumors are KRAS wild-type.

These findings, reported in The New England Journal of Medicine for April 2, are from a study of 1198 patients who were randomized to receive FOLFIRI alone or with cetuximab. All patients had EGF receptor-positive disease and metastatic disease that could not be cured by resection.

Although overall survival did not differ significantly between the groups, the risk of progression was 15% less in patients given cetuximab (p = 0.048), lead author Dr. Eric Van Cutsem, from University Hospital Gasthuisberg, Leuven, Belgium, and colleagues note.

Median progression-free survival times were 8.9 months with cetuximab plus FOLFIRI and 8.0 months with FOLFIRI alone, they report.

As noted, KRAS mutation status significantly influenced the tumor response (p = 0.03). In subjects with wild-type-KRAS tumors, treatment with cetuximab increased the odds of progression-free survival by 32%. In these patients, median progression-free survival was 9.9 months with cetuximab and 8.7 months with FOLFIRI alone.

In the mutant-KRAS population, however, median progression-free survival was 7.6 months with cetuximab plus FOLFIRI and 8.1 months with FOLFIRI alone.

Grade 3 skin reactions, infusion-related reactions, and diarrhea were all significantly more common with cetuximab plus FOLFIRI.

This trial provides confirmation that, as compared with FOLFIRI alone, cetuximab plus FOLFIRI reduces the risk of progression of metastatic colorectal cancer when used as the first-line treatment and that this benefit is seen mainly in patients with wild-type-KRAS tumors, the authors conclude.

Reference:
N Engl J Med 2009;360:1408-1417.

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