Cotellic (cobimetinib) is indicated in combination with vemurafenib (Zelboraf) for the treatment of unresectable or metastatic melanoma in patients with a BRAF V600 mutation.
Cobimetinib is a reversible allosteric inhibitor of mitogen-activated extracellular signal regulated kinases MEK1 and MEK2, components of the mitogen-activated protein kinase (MAPK) pathway. The combined modes of action of vemurafenib (a BRAF inhibitor) and cobimetinib lead to inhibition of intracellular MAPK signalling and decreased tumour cell proliferation.
Cotellic is given in a 28-day cycle consisting of 60mg once daily for the first 21 days, followed by a 7-day treatment-free period. Treatment should continue until benefit is no longer derived or toxicity becomes unacceptable.
In the phase III coBRIM study in 495 patients with previously untreated unresectable locally advanced or metastatic BRAF V600 mutation-positive melanoma, median progression-free survival was 9.9 months among those who received vemurafenib and cobimetinib, compared with 6.2 months in those who received vemurafenib and placebo (hazard ratio for death or disease progression 0.51, 95% CI 0.39–0.68; p<0.001).
In clinical trials, serous retinopathy occurred in more than 10% of patients treated with cobimetinib. Patients reporting new or worsening visual disturbances should be referred for an ophthalmologic examination. Treatment discontinuation, interruption or dose reduction should be considered if a diagnosis of serous retinopathy is confirmed.