Cobimetinib — Drug Monograph

Brand names: Cotellic

Drug class: Tyrosine Kinase Inhibitor

Mechanism of Action

Cobimetinib is an orally bioavailable, highly selective, reversible inhibitor of MEK1 and MEK2. These kinases are critical components of the RAS/RAF/MEK/ERK signaling pathway. By inhibiting MEK, cobimetinib prevents the phosphorylation of ERK and inhibits downstream signaling that would otherwise promote tumor cell proliferation and survival. It is used to overcome or delay resistance that develops with BRAF inhibitor monotherapy in BRAF V600 mutation-positive cancers.

FDA Indications

• In combination with vemurafenib, for the treatment of patients with unresectable or metastatic melanoma with a BRAF V600E or V600K mutation
• Treatment of adult patients with histiocytic neoplasms

Common Side Effects

• Diarrhea
• Photosensitivity reaction
• Nausea
• Pyrexia
• Vomiting
• Stomatitis
• Increased CPK
• Hypophosphatemia
• Increased ALT/AST
• Anemia

Clinical Pearl

A distinguishing feature of cobimetinib is its intermittent dosing schedule (21 days on, 7 days off) when used for melanoma, which differs from the continuous dosing of other MEK inhibitors. Photosensitivity is a very common and significant side effect; patients must be counseled on aggressive sun protection. When used in combination with vemurafenib, it reduces the incidence of vemurafenib-induced cutaneous squamous cell carcinomas but adds risk for serous retinopathy. It has recently gained…

Related Therapies & Mechanisms

• Binimetinib (Mektovi) — Tyrosine Kinase Inhibitor · Melanoma
• Dabrafenib (Tafinlar) — Tyrosine Kinase Inhibitor · Melanoma
• Encorafenib (Braftovi) — Tyrosine Kinase Inhibitor · Melanoma
• Trametinib (Mekinist) — Tyrosine Kinase Inhibitor · Melanoma