Newly Diagnosed mCRC Treatment Goals

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The frontline treatment of patients with metastatic colorectal cancer (mCRC) is largely dependent on upfront RAS mutation status, explains Marwan G. Fakih, MD. Traditionally, KRAS testing was utilized in this space; however, recent evidence suggests that RAS could be more predictive of response.

A biomarker analysis of the phase III PRIME study that was published in the New England Journal of Medicine showed that narrowing down treatment with panitumumab to patients with only RAS wild-type mutations resulted in an improvement in overall survival (OS) of 5.8 months.

The median OS with panitumumab was 26.0 months compared with 20.2 months with FOLFOX alone in patients with wild-type RAS (HR = 0.78; P = .04). Patients with RAS mutations had a 3.6-month worse median OS with panitumumab compared with FOLFOX alone (15.6 vs 19.2 months; HR = 1.25; P = .04).

In addition to expanded RAS testing, Fakih typically orders BRAF testing, since these mutations are associated with distinct clinical characteristics and worse prognosis. Other important considerations include whether the intent of therapy is curative or palliative, age, performance status, and pattern of metastatic disease.