FDA Approves New Combination for BRAF V600E-Mutated Colorectal Cancer

The U.S. Food and Drug Administration (FDA) approved Braftovi® (encorafenib) in combination with cetuximab for previously treated patients with metastatic colorectal cancer (CRC) with the BRAF V600E mutation, as detected by the FDA-approved Qiagen therascreen® BRAF V600E RGQ PCR kit.

The decision was based on results of the randomized, active-controlled, open-label, multicenter, phase III BEACON CRC trial that included patients with BRAF V600E mutation-positive metastatic CRC whose disease progressed after one or two prior therapies. Patients were randomized to receive encorafenib 300 mg orally once daily in combination with cetuximab (n=220) or either irinotecan or FOLFIRI plus cetuximab (control group; n=221).

Improved survival with the addition of encorafenib

Median overall survival (major efficacy outcome) was 8.4 months in the encorafenib and cetuximab arm compared with 5.4 months in the control group (hazard ratio [HR], 0.60; 95% CI, 0.45-0.79; P=0.0003). Median progression-free survival was 4.2 months versus 1.5 months, respectively (HR, 0.40; 95% CI, 0.31-0.52; P<0.0001). Overall response rate was 20% and 2%, respectively. Median duration of response was 6.1 months in the encorafenib and cetuximab group and not reached in the control arm.

The most common adverse events associated with encorafenib plus cetuximab were fatigue, nausea, diarrhea, dermatitis acneiform, abdominal pain, decreased appetite, arthralgia, and rash.

Full results of the trial were published in The New England Journal of Medicine.