Amgen (NASDAQ: AMGN) today announced the publication of 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 ('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.
In patients with wild-type RAS, OS was 26.0 months and 20.2 months (HR = 0.78; 95 percent CI, 0.62-0.99) and PFS was 10.1 months and 7.9 months (HR = 0.72, 95 percent 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 percent CI, 1.02-1.55) and PFS (HR = 1.34, 95 percent 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.
"Amgen is proud of our continuing work to identify and establish predictive biomarkers, like RAS, that will help better inform therapeutic decisions," said Sean E. Harper, M.D., executive vice president of Research and Development at Amgen. "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."
No new safety signals were identified in this analysis.
PRIME ('203) Study Design
The PRIME (Panitumumab Randomized trial In combination with chemotherapy for Metastatic colorectal cancer to determine Efficacy) ('203) trial is a global, multicenter, randomized Phase 3 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. The primary endpoint is PFS.
The primary objective of this predefined retrospective subset analysis was to determine the effect of Vectibix plus FOLFOX versus FOLFOX alone on OS and PFS in patients with mCRC based on RAS or BRAF mutation status. The analysis included 512 patients who were identified with wild-type RAS tumors.
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