Cobimetinib, sold under the brand name Cotellic, is an anti-cancer medication used in combination with vemurafenib (Zelboraf) alone or with both vemurafenib and

atezolizumab Atezolizumab, sold under the brand name Tecentriq, is a monoclonal antibody medication used to treat urothelial carcinoma, non-small cell lung cancer (NSCLC), triple-negative breast cancer (TNBC), small cell lung cancer (SCLC), hepatocellula ...

(Tecentriq) to treat

melanoma Melanoma, also redundantly known as malignant melanoma, is a type of skin cancer that develops from the pigment-producing cells known as melanocytes. Melanomas typically occur in the skin, but may rarely occur in the mouth, intestines, or eye ( ...

. Cobimetinib is a MEK inhibitor. Cotellic, Zelboraf, and Tecentriq are all marketed by

Genentech Genentech, Inc., is an American biotechnology corporation headquartered in South San Francisco, California. It became an independent subsidiary of Roche in 2009. Genentech Research and Early Development operates as an independent center within ...

. The most common side effects include diarrhea, rash, nausea (feeling sick), vomiting, pyrexia (fever), photosensitivity (light sensitivity) reaction, abnormal results for certain liver function tests (increased levels of alanine aminotransferase, aspartate aminotransferase) and abnormal results for an enzyme related to muscle breakdown (creatine phosphokinase). Cobimetinib was approved for medical use in the United States in November 2015.

Medical use

Cobimetinib is approved for use in combination with vemurafenib for the treatment of advanced

with BRAF mutation (either V600E or V600K) that cannot be removed by surgery or which has metastasized. In the European Union, cobimetinib is indicated for use in combination with vemurafenib for the treatment of adults with unresectable or metastatic melanoma with a BRAF V600 mutation. Text was copied from this source which is © European Medicines Agency. Reproduction is authorized provided the source is acknowledged.

Atezolizumab Atezolizumab, sold under the brand name Tecentriq, is a monoclonal antibody medication used to treat urothelial carcinoma, non-small cell lung cancer (NSCLC), triple-negative breast cancer (TNBC), small cell lung cancer (SCLC), hepatocellula ...

in combination with cobimetinib and vemurafenib is indicated for the treatment of people with BRAF V600 mutation-positive unresectable or metastatic melanoma.

Adverse effects

Common adverse effects observed in cobimetinib and vemurafenib co-treated persons in clinical trials included diarrhea, nausea, vomiting, rash, photosensitivity, and

pyrexia Fever, also referred to as pyrexia, is defined as having a temperature above the normal range due to an increase in the body's temperature set point. There is not a single agreed-upon upper limit for normal temperature with sources using va ...

History

Cobimetinib was granted

orphan drug status An orphan drug is a pharmaceutical agent developed to treat medical conditions which, because they are so rare, would not be profitable to produce without government assistance. The conditions are referred to as orphan diseases. The assignment of ...

by the US

Food and Drug Administration The United States Food and Drug Administration (FDA or US FDA) is a federal agency of the Department of Health and Human Services. The FDA is responsible for protecting and promoting public health through the control and supervision of food ...

(FDA) for

malignant melanoma Melanoma, also redundantly known as malignant melanoma, is a type of skin cancer that develops from the pigment-producing cells known as melanocytes. Melanomas typically occur in the skin, but may rarely occur in the mouth, intestines, or eye ...

with BRAFV600 mutation in 2014, and for histiocytic neoplasms in 2021. Acquired resistance to BRAF inhibitors, such as vemurafenib and dabrafenib, commonly occurs after several months of progression-free tumor response. Preclinical data indicated the involvement of

MAPK A mitogen-activated protein kinase (MAPK or MAP kinase) is a type of protein kinase that is specific to the amino acids serine and threonine (i.e., a serine/threonine-specific protein kinase). MAPKs are involved in directing cellular responses to ...

pathways and MAPK-independent signaling in the developed resistance, suggesting dual inhibition of MEK and BRAF kinase as a strategy for increasing the longevity of tumor response seen with BRAF inhibition alone. In phase III clinical trials, the combination of cobimetinib and vemurafenib was tested in patients with BRAFV600-mutated metastatic melanoma, which resulted in significant improvement in progression-free survival in patients, but also produced some increase in toxicity. The combination increased progression-free survival to an average of 12.3 months, compared to 7.2 months for vemurafenib alone. This clinical data also showed that the combination treatment resulted in 65% survival rate of patients 17 months after beginning the treatment, increased rates from the 50% of patients on vemurafenib treatment alone. Adding cobimetinib also increased the median overall survival to 25.6 months, compared to the 18 months for vemurafenib alone. Pre-clinical investigation suggests that combined use of cobimetinib with

PI3K Phosphoinositide 3-kinases (PI3Ks), also called phosphatidylinositol 3-kinases, are a family of enzymes involved in cellular functions such as cell growth, proliferation, differentiation, motility, survival and intracellular trafficking, which i ...

inhibition could boost the anti-cancer effects of the drug, with a synergistic response being observed in lung cancer cell lines. The U.S.

(FDA) approved cobimetinib based on evidence from one clinical trial of 495 participants with melanoma containing the BRAF V600 mutation that was advanced or could not be removed by surgery. The trial was conducted at 133 sites in 19 countries including those in North America, Europe, and Australia.

References

External links

* * {{Portal bar , Medicine Azetidines Benzamides Experimental cancer drugs Fluoroarenes Iodoarenes MEK inhibitors Piperidines Protein kinase inhibitors Hoffmann-La Roche brands Genentech brands Orphan drugs