BRAF mutations occur in approximately 15% of patients with metastatic colorectal cancer (mCRC) and are associated with a poor prognosis and limited treatment options. On April 8, 2020, the US FDA announced approval of the BRAF inhibitor encorafenib in combination with the EGFR inhibitor cetuximab as treatment for patients with BRAF V600E-mutated mCRC who have progressed on prior therapy.
This approval was based on results from the randomized, open-label phase III BEACON trial, which compared the combination of encorafenib and cetuximab to standard chemotherapy in 665 patients with BRAF-mutated mCRC who had progressed on one or two prior regimens. The combination of encorafenib and cetuximab was associated with a median overall survival (OS) of 8.4 months, compared to 5.4 months in the chemotherapy arm (HR 0.60, P < .001). Median progression-free survival (PFS) was also improved with encorafenib and cetuximab (4.2 months vs 1.5 months; HR 0.4, P < .0001). The objective response rate (ORR) was 20% with encorafenib plus cetuximab and 2% with chemotherapy. Rates of adverse events (AEs) of grade 3 or higher were similar in the encorafenib plus cetuximab and chemotherapy arms (50% vs 61%). The most common AEs associated with encorafenib and cetuximab are fatigue, nausea, diarrhea, dermatitis acneiform, abdominal pain, decreased appetite, arthralgia, and rash.
The BEACON trial also evaluated triplet therapy with the combination of encorafenib, binimetinib, and cetuximab, but there was no additional therapeutic benefit with the addition of binimetinib and the FDA approval does not extend to this combination.
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