ENCORAFENIB/CETUXIMAB APPROVED FRO BRAF V600E COLORECTAL CANCER

On April 8, the U.S. Food and Drug Administration (FDA) approved encorafenib (Braftovi) in combination with cetuximab (Erbitux) for the treatment of pretreated adult patients with metastatic colorectal cancer with a BRAF V600E mutation detected by an FDA-approved test.

BEACON CRC

Efficacy was evaluated in the randomized, active-controlled, open-label, multicenter BEACON CRC trial. Eligible patients were required to have BRAFV600E mutation–positive metastatic colorectal cancer (detected by the Qiagen therascreen BRAF V600E RGQ PCR kit) with disease progression after one or two prior regimens. A total of 220 patients were randomly assigned to receive encorafenib at 300 mg orally once daily in combination with cetuximab; 221 patients were randomly assigned to the control arm of either irinotecan or FOLFIRI with cetuximab.

The major efficacy outcome measure was overall survival; additional efficacy outcome measures included progression-free survival, overall confirmed response rate, and duration of response. Overall response rate and duration of response were assessed by blinded independent central review in the subset of the first 220 patients assigned to receive either encorafenib plus cetuximab or the control arm.

Results

Median overall survival was 8.4 months (95% confidence interval [CI] = 7.5–11.0) in the encorafenib/cetuximab arm compared to 5.4 months (95% CI = 4.8–6.6) in the control arm (HR = 0.60, 95% CI = 0.45–0.79, P = .0003). Median progression-free survival was 4.2 months (95% CI = 3.7–5.4) in the encorafenib/cetuximab arm compared to 1.5 months (95% CI = 1.4–1.7) in the control arm (HR = 0.40, 95% CI = 0.31–0.52, P < .0001). Overall response rate was 20% (95% CI = 13%–29%) and 2% (95% CI = 0%–7%), respectively. Median duration of response was 6.1 months (95% CI = 4.1–8.3) for the encorafenib/cetuximab arm and not reached (95% CI = 2.6–not reached) in the control arm.

The most common adverse reactions (≥ 25%) reported in patients treated with the doublet were fatigue, nausea, diarrhea, dermatitis acneiform, abdominal pain, decreased appetite, arthralgia, and rash.

The recommended encorafenib dose is 300 mg orally once daily in combination with cetuximab.