Amgen announced positive top-line results from a phase-3 trial evaluating Vectibix (panitumumab) in combination with Folfiri (an irinotecan-based chemotherapy) as a second-line treatment in 1,186 patients with metastatic colorectal cancer (mCRC). The co-primary endpoints, tested independently, were progression-free and overall survival.

Vectibix significantly improved progression-free survival in combination with Folfiri, compared to Folfiri alone, in patients with KRAS wild-type mCRC. Although numerically greater, the improvement in median overall survival did not achieve statistical significance in the Vectibix arm.

The addition of Vectibix had no positive or negative effect on progression-free or overall survival in patients with tumours harbouring activating KRAS mutations.

"With these data, Vectibix has now demonstrated improved progression-free survival in phase-3 trials in patients with KRAS wild-type tumours in both first- and second-line treatment of metastatic colorectal cancer," said Roger M Perlmutter, executive vice president of Research and Development at Amgen. "These results add to the growing body of evidence confirming the utility of KRAS as a predictive biomarker."

Overall, the adverse event profile was as anticipated for an anti-EGFR antibody in combination with irinotecan-based chemotherapy, including known events such as skin toxicity, diarrhoea and hypomagnesemia.

Originally designed to compare the treatment effect in the overall population, the study was amended to analyze outcomes with respect to the presence or absence of activating mutations in KRAS in the tumour itself. Tumour KRAS status was ascertained in more than 90 percent of patients enrolled in this trial.

Recently, the company announced phase-3 results from a first-line '203' trial which showed that Vectibix significantly improved progression-free survival in mCRC patients with KRAS wild-type tumors in combination with FOLFOX (an oxaliplatin-based chemotherapy).

Detailed efficacy and safety data from both studies will be presented at Europe's largest cancer conference, ECCO 15 - ESMO 34, in September 2009.

Results from studies performed over the last twenty-five years indicate that KRAS plays an important role in cell growth regulation.