cobimetinib

Cobimetinib is a selective inhibitor of the mitogen-activated protein kinase kinase (MEK) 1 and 2 enzymes, a component of the MAPK/ERK signaling pathway. It is a small-molecule anticancer drug developed by Roche and is marketed in combination with the BRAF inhibitor vemurafenib under the brand name Cotellic.

In tumors with BRAF V600 mutations, the MAPK pathway is constitutively active and promotes cancer cell growth. Cobimetinib binds to MEK1/2 and inhibits their phosphorylation of ERK, thereby reducing tumor cell proliferation and promoting apoptosis in BRAF-mutant cells when used with a BRAF inhibitor. The combination aims to counteract resistance mechanisms that arise with BRAF inhibition alone.

Indications and regulatory status: Cobimetinib is approved for use in adults in combination with vemurafenib for unresectable or metastatic melanoma whose tumors carry a BRAF V600 mutation. The combination therapy is intended to address disease progression and overcome resistance to BRAF inhibition in selected patients.

Dosing and administration: In the approved regimen, cobimetinib is given orally at 60 mg once daily on days 1–21 of a 28-day cycle, while vemurafenib is administered at 960 mg twice daily. Dosing can be adjusted or interrupted based on tolerability and adverse events, and the regimen is supervised by clinicians experienced in cancer therapy.

Adverse effects and safety: Common adverse events include diarrhea, nausea, vomiting, rash, photosensitivity, fatigue, edema, and headache. Ocular toxicity, such as retinopathy or serous retinal detachment, can occur, along with hepatotoxicity and wound-healing impairment. Serious events are monitored and managed with dose adjustments or discontinuation as needed.

See also: MEK inhibitors and other targeted therapies for BRAF-mutant melanoma.