Merck KGaA’s cancer drug Erbitux was unable to improve overall survival when used as a second-line treatment for metastatic colorectal cancer in the Phase III EPIC trial, although a second study looking at its use as a third-line therapy did meet that objective.

The German company insists that positive findings on progression-free survival and response rates in EPIC are clinically significant and support the use of Erbitux (cetuximab) in these patients.

It noted that a considerable number of patients in the irinotecan arm of EPIC who had progressed on their therapy subsequently received Erbitux plus irinotecan, a highly active treatment, and this may have made it harder for an effect on overall survival to be seen.

“These are the first data of an EGFR targeted antibody to demonstrate overall survival in the third-line treatment setting,” said Merck, claiming that the data differentiate Erbitux from other drugs that block this molecular target.

Meanwhile, in the second study - the 572-patient NCIC-CO.17 trial – Erbitux was able to show an improvement on survival when given as a monotherapy after failure of earlier treatment with irinotecan, oxaliplatin and fluoropyrimidines.

The updated results from the EPIC and NCIC-CO.17 trials “clearly demonstrate the activity of Erbitux in the treatment of metastatic colorectal cancer. It is well known that survival differences are difficult to achieve in diseases where multiple lines of active treatments are available,” said Dr Wolfgang Wein, senior vice president, global oncology commercialisation at Merck.

However, analysts are concerned that missing the primary endpoint may make it harder for Merck to convince European regulators to expand Erbitux’ labelling at a time when the drug is facing competition from Roche/Genentech’s Avastin (bevacizumab) and - in the USA – Amgen’s new Vectibix (panitumumab) product.

Missing the primary endpoint of EPIC also comes at a sensitive time with healthcare payers in a number of countries, including the UK, discussing reimbursement of the drug.

That said, the battleground for biologic treatments for colorectal cancer is expected to be in first-line treatment, and Merck noted that the improvement in progression-free survival in EPIC is very important for the ongoing CRYSTAL study currently underway in the first-line setting, which has progression-free survival as the primary endpoint.