Encorafenib — Drug Monograph

Brand names: Braftovi

Drug class: Tyrosine Kinase Inhibitor

Mechanism of Action

Encorafenib is a kinase inhibitor that targets BRAF V600E, as well as wild-type BRAF and CRAF in cell-free in vitro assays. It inhibits the MAP kinase signaling pathway by binding to the V600E mutated BRAF kinase, which leads to decreased proliferation and increased apoptosis in cells expressing this mutation. Compared to other BRAF inhibitors, encorafenib has a longer dissociation half-life (>30 hours), leading to sustained inhibition of the pathway. It is utilized in combination with MEK inhibitors or EGFR inhibitors to overcome bypass signaling.

FDA Indications

• In combination with binimetinib, for the treatment of patients with unresectable or metastatic melanoma with a BRAF V600E or V600K mutation, as detected by an FDA-approved test
• In combination with cetuximab, for the treatment of adult patients with metastatic colorectal cancer (CRC) with a BRAF V600E mutation, as detected by an FDA-approved test, after prior therapy
• In combination with binimetinib, for the treatment of adult patients with metastatic non-small cell lung cancer (NSCLC) with a BRAF V600E mutation, as detected by an FDA-approved test

Common Side Effects

• Fatigue
• Nausea
• Vomiting
• Abdominal pain
• Arthralgia
• Myopathy
• Hyperkeratosis
• Rash
• Dry skin
• Hand-foot syndrome

Clinical Pearl

Encorafenib is uniquely indicated for BRAF V600E-mutant metastatic colorectal cancer in combination with cetuximab (the BEACON regimen). This is based on the discovery that BRAF inhibition in CRC causes rapid feedback activation of EGFR, necessitating dual blockade. When used for melanoma, the 450 mg dose is higher than the 300 mg dose used for CRC. It generally has a lower incidence of pyrexia compared to dabrafenib and a lower incidence of photosensitivity compared to vemurafenib.

Related Therapies & Mechanisms

• Binimetinib (Mektovi) — Tyrosine Kinase Inhibitor · Melanoma
• Cobimetinib (Cotellic) — Tyrosine Kinase Inhibitor · Melanoma
• Dabrafenib (Tafinlar) — Tyrosine Kinase Inhibitor · Melanoma
• Fruquintinib (Fruzaqla) — Tyrosine Kinase Inhibitor · CRC