PRIME Trial: RAS Mutations in Metastatic Colorectal Cancer

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The molecular characterization of metastatic colorectal cancer (mCRC) continues to evolve as more information is gathered from clinical trials. This is demonstrated by a retrospective biomarker analysis from the phase III PRIME study, which was recently published in the New England Journal of Medicine.

In the study, FOLFOX plus panitumumab was compared to panitumumab alone for patients with mCRC based on RAS or BRAF mutation status. The biomarker analysis examined patients with KRAS exons 2, 3, 4, and NRAS mutations separately for each arm of the trial. As a result of narrowing down treatment with panitumumab to patients with only RAS wild-type mutations, overall survival (OS) was improved by an additional 5.8 months, explains Tanios Bekaii-Saab, MD. The analysis also found that BRAF mutations do not have a predictive value for EGFR inhibitors.

This analysis mandates that a new approach should be taken for selecting appropriate patients for EGFR inhibitors, notes Axel Grothey, MD. Not only does selecting for these added mutations increase the likelihood of benefit but it also decreases the chances of doing harm. In the study, patients with RAS mutations were found to have inferior OS with panitumumab plus FOLFOX compared to FOLFOX alone. As a result, there is a clear need for more sophisticated assays to select patients for treatment with EGFR inhibitors, Grothey notes.

The leading molecular testing concerns in the community setting are reimbursement and time, explains Fadi Braiteh, MD, CPI. Additionally, he believes, nomenclature needs to be adjusted to be more specific, such as exact exons in KRAS. Moreover, Braiteh believes, guidelines should be adjusted to help specific the type of technology to use for molecular testing, whether that be PCR or next generation sequencing.

Determining the best treatment is not always a black and white situations, notes Alan P. Venook, MD. It is often hard to avoid treatments that cause some adverse effects when consulting with a patient the treatment selected often depends on individual factors, Venook adds.