Plenary Study Links KRAS Status to Effectiveness of Cetuximab in Colon Cancer Patients

June 1, 2008

A new analysis of a randomized, controlled clinical trial investigating cetuximab (Erbitux) in the treatment of first-line metastatic colorectal cancer (mCRC) highlights the increased efficacy of cetuximab in patients who have tumors with nonmutated (ie, wild-type) KRAS. These results were presented by lead investigator Eric Van Cutsem, md, phd, professor of medicine and digestive oncology from the University Hospital Gasthuisberg in Leuven, Belgium, at the plenary session of the 44th Annual Meeting of the American Society for Clinical Oncology (ASCO), held May 30 through June 3 in Chicago (abstract 2).

A new analysis of a randomized, controlled clinical trial investigating cetuximab (Erbitux) in the treatment of first-line metastatic colorectal cancer (mCRC) highlights the increased efficacy of cetuximab in patients who have tumors with nonmutated (ie, wild-type) KRAS. These results were presented by lead investigator Eric Van Cutsem, md, phd, professor of medicine and digestive oncology from the University Hospital Gasthuisberg in Leuven, Belgium, at the plenary session of the 44th Annual Meeting of the American Society for Clinical Oncology (ASCO), held May 30 through June 3 in Chicago (abstract 2).

CRYSTAL Trial

The new analysis from the phase III CRYSTAL trial found that patients with KRAS wild-type tumors treated with cetuximab in combination with standard chemotherapy in the first-line setting experienced significantly enhanced efficacy compared to those bearing a KRAS mutation. Patients with KRAS wild-type tumors experienced significantly increased response rates and significantly decreased risk of progression compared to the patients with a KRAS mutation in their tumors.

The previously reported CRYSTAL study investigated cetuximab in combination with the standard chemotherapy regimen FOLFIRI (fluorouracil, leucovorin, irinotecan) in 540 mCRC patients. This new analysis found that the addition of cetuximab in patients with KRAS wild-type tumors led to:

• A significant increase in response rate up to 59% compared to 43% for those receiving FOLFIRI alone (P = .0025)

• A 32% decrease in risk of progression (hazard ratio = 0.68; P = .017), which was also reflected in a statistically significant higher progression-free survival compared to patients receiving FOLFIRI alone (43% vs 25% at 1 year).

‘Real Advance’ in First-Line Treatment

“These results are extremely exciting. They are the first biomarker data from major studies in the first-line setting, which clearly demonstrate the increased efficacy of Erbitux in combination with standard chemotherapy in patients who have wild-type KRAS tumors,” commented Professor Van Cutsem. “The chance that these patients would be alive after 1 year without tumor growth nearly doubled compared to those receiving irinotecan-based chemotherapy alone. This is a real advance in first-line mCRC treatment.”