Binimetinib — Drug Monograph

Brand names: Mektovi

Drug class: Tyrosine Kinase Inhibitor

Mechanism of Action

Binimetinib is a reversible inhibitor of mitogen-activated extracellular signal-regulated kinase 1 (MEK1) and MEK2. MEK proteins are upstream regulators of the extracellular signal-related kinase (ERK) pathway, which promotes cellular proliferation and survival. By inhibiting MEK1/2, binimetinib blocks the activation of ERK and inhibits the growth of BRAF-mutant tumor cells. It is specifically used to target the MAPK pathway in conjunction with BRAF inhibitors.

FDA Indications

• In combination with encorafenib, 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 encorafenib, 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
• Diarrhea
• Vomiting
• Abdominal pain
• Arthralgia
• Myopathy
• Increased Creatine Phosphokinase (CPK)
• Visual disturbances
• Dizziness
• Peripheral edema

Clinical Pearl

Binimetinib is almost exclusively used in combination with encorafenib to provide dual blockade of the MAPK pathway. This combination is generally better tolerated from a skin toxicity perspective than earlier BRAF/MEK combinations (like dabrafenib/trametinib), showing lower rates of pyrexia. However, clinicians must be vigilant about asymptomatic increases in CPK and potential ocular toxicities like serous retinopathy. Dose interruptions for CPK elevations are common but binimetinib can often…

Related Therapies & Mechanisms

• Cobimetinib (Cotellic) — Tyrosine Kinase Inhibitor · Melanoma
• Dabrafenib (Tafinlar) — Tyrosine Kinase Inhibitor · Melanoma
• Encorafenib (Braftovi) — Tyrosine Kinase Inhibitor · Melanoma
• Trametinib (Mekinist) — Tyrosine Kinase Inhibitor · Melanoma