Amgen has published a biomarker analysis of Vectibix (panitumumab) in combination with FOLFOX, a type of oxaliplatin-based chemotherapy, for the first-line treatment of patients with metastatic colorectal cancer (mCRC). Published in the New England Journal of Medicine, the analysis found that RAS mutations, beyond the known KRAS exon 2 mutations, predict lack of response to Vectibix in combination with FOLFOX. RAS mutations are mutations occurring in exons 2, 3 and 4 of KRAS and NRAS.

"While the KRAS exon 2 biomarker is well-known and has facilitated selection of patients more likely to respond to anti-EGFR treatment, we found that there were still some patients who didn't benefit from treatment," said Jean-Yves Douillard, M.D., Ph.D., professor of medical oncology, Centre R Gauducheau, France and PRIME trial lead investigator and study author. "This analysis is important as it furthers our understanding of tumor genetics and allows physicians to more accurately match patients to effective treatments."

This predefined retrospective subset analysis of the PRIME (Panitumumab Randomized trial In combination with chemotherapy for Metastatic colorectal cancer to determine Efficacy) ('203) study assessed the safety and efficacy of Vectibix plus FOLFOX, compared to FOLFOX alone based on RAS or BRAF mutation status. By more precisely narrowing the pool of patients treated with Vectibix plus FOLFOX to those with wild-type RAS, greater improvements in overall survival (OS) and progression-free survival (PFS) were observed. Specifically, previous data found that OS was improved by 4.4 months in patients with wild-type KRAS. By further narrowing to patients with wild-type RAS, an improvement in OS of 5.8 months was observed.

The PRIME trial is a global, multicenter, randomized phase III study designed to evaluate Vectibix (6.0 mg/kg every two weeks) plus FOLFOX versus FOLFOX alone in patients with wild-type KRAS exon 2 mCRC.

In patients with wild-type RAS, OS was 26 months and 20.2 months (HR = 0.78; 95% CI, 0.62-0.99) and PFS was 10.1 months and 7.9 months (HR = 0.72, 95% CI, 0.58-0.90) in the Vectibix plus FOLFOX arm compared to the FOLFOX alone arm, respectively. BRAF mutations were not observed to have predictive value.

Conversely, in the patients with RAS mutations, inferior OS (HR = 1.25, 95% CI, 1.02-1.55) and PFS (HR = 1.34, 95% CI, 1.07-1.60) were observed in the Vectibix plus FOLFOX arm compared to the FOLFOX alone arm.

Amgen has informed investigators and physicians of this important new safety information, and is working with regulatory agencies regarding appropriate communication of the outcomes of the analysis.

"As a result of this information, the European Commission has refined the prescribing information for Vectibix to the treatment of adult patients with wild-type RAS metastatic colorectal cancer," said Sean E. Harper, M.D., executive vice president of R&D at Amgen.