A small molecule BRAF inhibitor that targets key enzymes in the MAPK signaling pathway.
Approved by the FDA in combination with binimetinib for the treatment of patients with unresectable or metastatic BRAF V600E or V600K mutation-positive melanoma.
Acts as an ATP-competitive RAF kinase inhibitor, decreasing ERK phosphorylation and down-regulation of CyclinD1.
It arrests the cell cycle in G1 phase, inducing senescence without apoptosis.
Only effective in melanomas with a BRAF mutation, which make up 50% of all melanomas.
The plasma elimination half-life is approximately 6 hours.
Metabolism occurs via cytochrome P450 enzymes.
The combination of a BRAF/MEK kinases have been approved for his treatment of patients with metastatic melanoma that is unresectable.
Encorafenib/binimetinib combination for a BRAF mutational melanoma ( Braftovi/Mektovi).
There is approval of the targeted drug encorafenib in combination with another targeted therapy, cetuximab (Erbitux) for some patients with colorectal cancer whose tumors have a specific mutation in the BRAF gene, called V600E, and who have already undergone at least one prior treatment regimen.
The V600E mutation in the BRAF gene is found in about 10% of metastatic colorectal cancers and is associated with especially poor outcomes.
The BEACON CRC trial was designed to test whether combining targeted therapies to simultaneously block multiple components of the BRAF signaling pathway could improve outcomes in patients with metastatic BRAF-mutant colorectal cancer.
Patients who received encorafenib and cetuximab had a median overall survival of 8.4 months compared with 5.4 months for patients in the control arm.
Patients who received the two-drug combination had a tumor response than patients in the control arm: 20% versus 2%.
The most common severe side effects in patients treated with encorafenib and cetuximab included fatigue and weakness, nausea, rash, and diarrhea.