Cobimetinib in melanoma with BRAF V600 mutation: Indication of minor added benefit

Source: EurekAlert, March 2016

Cobimetinib (trade name: Cotellic) has been approved since November 2015 in combination with vemurafenib for the treatment of adults with advanced, i.e. metastatic or unresectable, melanoma with a BRAF V600 mutation. The Federal Joint Committee (G-BA) therefore commissioned the German Institute for Quality and Efficiency in Health Care (IQWiG) to examine whether cobimetinib in combination with vemurafenib has an added benefit over the appropriate comparator therapy vemurafenib alone.

IQWiG found positive and negative effects for several patient-relevant outcomes, which did not completely outweigh one another: An indication of a minor added benefit of the new drug combination compared with vemurafenib monotherapy remained.

Drugs inhibit enzymes of the MAP kinase signal pathway

In about half of all melanomas, the gene for the BRAF enzyme is mutated, which belongs to the MAP kinase signal pathway and which, in its changed form, contributes to increased cell proliferation. Drugs such as vemurafenib inhibit the activity of the mutated BRAF kinase. However, many melanomas develop resistance after some time; they bypass the blocked MAP kinase pathway. A second inhibitor targeting a different site is used to lower this risk: Cobimetinib inhibits the MEK enzyme, which follows BRAF in the signal pathway.