Adding the targeted drug Cetuximab ( Erbitux ) to a three-drug chemotherapy regimen for first-line treatment of metastatic colorectal cancer does not improve response rate, progression-free survival or overall survival.

NORDIC VII study included 566 patients who were randomly assigned to either a combination of 5-Fluorouracil plus Folinate plus Oxaliplatin ( NORDIC FLOX ), FLOX plus Cetuximab until disease progression, or FLOX intermittently plus continuous Cetuximab.

The finding that Cetuximab did not add any significant benefit to the FLOX regimen ( Fluorouracil, Folinate and Oxaliplatin ) was unexpected.
Cetuximab has a documented beneficial effect in later stages of metastatic colorectal cancer, when given alone or together with chemotherapy. Researchers expected that similar findings would be found in early stage when given together with an Oxaliplatin regimen.

Among the whole study population, there were no statistically significant differences between the treatment groups in terms of response rate, progression-free survival or overall survival.

The lack of significant benefit also applied to sub-groups of patients with mutant and wild-type versions of the KRAS gene.
Some recent studies have shown that the beneficial effect of Cetuximab was limited to the group of patients without KRAS-mutations.

The new results come after mixed results from trials in which Cetuximab was added to chemotherapy as first-line treatment in colorectal cancer. In the Phase-III CRYSTAL study, Cetuximab combined with an Irinotecan-based combination known as FOLFIRI had a positive effect. Similarly, Cetuximab was beneficial when combined with FOLFOX in the Phase-II OPUS study.

However, the Phase-III COIN study, also using Oxaliplatin combination as standard, did not show a positive effect of adding Cetuximab.

The results do not support the use of Cetuximab in first line when given together with an Oxaliplatin regimen. The results of trials combining Cetuximab with an Irinotecan regimen, as well as results from Panitumumab studies in first line, seem to be more positive. However, researchers have concluded that these drugs are not fully established as part of standard first-line treatment of metastatic colorectal cancer.

Source: ESMO Meeting, 2010

XagenaMedicine2010


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