Human medicines European public assessment report (EPAR): Braftovi, encorafenib, Date of authorisation: 19/09/2018, Revision: 18, Status: Authorised

Vemurafenib is an oral small molecule inhibitor that targets BRAF V600-mutant tumors and has significant anti-tumor efficacy. However, attention should be paid to potential side effects and safety issues during its use.

Bimetinib is an inhibitor of the MEK signaling pathway. Inhibiting MEK activity can block downstream pathways and suppress abnormal activation caused by upstream gene mutations, thereby exerting an anti-tumor effect.

Cannefenib is a prescription drug approved by the U.S. Food and Drug Administration (FDA) in 2018. It is used for BRAF V600E and BRAF V600K gene mutations that require FDA approval for testing confirmation. It should be used strictly in accordance with your doctor's instructions.

Binimetinib is a selective inhibitor of MEK, a centrally acting kinase in the tumor-promoting MAPK pathway, which has been shown to be inappropriately activated in many cancers. In June 2018, the FDA approved it in combination with encorafenib for the treatment of patients with unresectable or metastatic BRAF V600E or V600K mutation-positive melanoma.

Vemurafenib induces programmed apoptosis in melanoma cell lines. If B-Raf has the common V600E mutation, vemurafenib disrupts the B-Raf/MEK step in the B-Raf/MEK/ERK pathway. Vemurafenib is only effective in melanoma patients with the V600E BRAF mutation. Approximately 60% of melanomas have this mutation. It is also effective against the rare BRAF V600K mutation. Melanoma cells without these mutations are not suppressed by vemurafenib; the drug paradoxically stimulates normal BRAF and may promote tumor growth in this case.

Encorafenib is a small molecule inhibitor of BRAF, a key enzyme in the MAPK signaling pathway. The MAPK pathway plays an important role in various cancers, including melanoma and colorectal cancer. Encorafenib is used in combination with binimetinib to treat patients with metastatic melanoma harboring BRAF mutations of V600E or V600K. The most common side effects (25%) include fatigue, nausea, diarrhea, abdominal pain, and joint pain.