Cobimetinib

Information about Cobimetinib

Cobimetinib is a tyrosine kinase receptor inhibitor that is used in combination with vemurafenib as therapy for selected forms of advanced malignant melanoma.

Liver safety of Cobimetinib

The combination of cobimetinib and vemurafenib is commonly associated with serum enzyme elevations during therapy and to rare instances of clinically apparent acute liver injury. 

Mechanism of action of Cobimetinib

Cobimetinib (koe" bi me' ti nib) is a small molecule tyrosine kinase receptor inhibitor with potent activity against the mitogen-activated extracellular regulated kinase (MEK), which is an important component of the kinase cascade in the mitogen activated protein kinase (MAPK) pathway (RAS-RAF-MEK-ERK).  Components of the MAPK pathways are frequently mutated in patients with malignant melanoma, particularly the RAF isoform BRAF.  BRAF-mutations cause a constitutive activation of the MAPK pathways, resulting in unregulated cell growth and proliferation.  Inhibition of MEK has been found to be synergistic when combined with specific BRAF inhibitors as therapy of BRAF-mutated cancers.  Clinical trials have shown that the addition of cobimetinib with vemurafenib (a specific BRAF-kinase inhibitor) results in improvements in survival in patients with melanoma who harbor the V600 BRAF mutation. 

FDA approval information for Cobimetinib

Cobimetinib received accelerated approval for use as combination therapy with vemurafenib in the United States in 2015.  Current indications are as combination therapy of metastatic or unresectable melanoma with BRAF V600E or V600K mutations. 

Dosage and administration for Cobimetinib

Cobimetinib is available in tablets of 20 mg under the brand name Cotellic.  The recommended dose is 60 mg once daily for the first 21 days of each 28-day cycle, continued until disease progression or intolerable toxicity occurs. 

Side effects of Cobimetinib

Side effects are common and include diarrhea, rash, photosensitivity, nausea, stomatitis, fever, alopecia and thrombocytopenia.  Uncommon, but potentially severe side effects include severe diarrhea leading to dehydration and renal failure, rhabdomyolysis, cardiac toxicity, retinal detachment and embryo-fetal toxicity.

 

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