Author: Anoma Ranaweera PhD, Medical Writer. Chief Editor: DermNet New Zealand Editor in Chief: Hon A/Prof Amanda Oakley, Dermatologist, Hamilton, New Zealand. Copy editor: Gus Mitchell, August 2017.
Cobimetinib is a prescription medicine that is used to treat a type of melanoma that has spread to other parts of the body, cannot be removed by surgery and has an abnormal BRAF gene. It should not used to treat melanoma in patients with a normal or “wild-type” BRAF gene.
In 2015, the US FDA (Food and Drug Administration) approved cobimetinib (Cotellic™, Genentech Inc. California, United States of America) in combination with vemurafenib (a specific BRAF-kinase inhibitor) for the treatment of melanoma.
In the same year, the Committee for Medicinal Products for Human Use (CHMP) at the European Medicines Agency (EMA) issued a positive opinion for marketing authorization for cobimetinib in the European Union.
Cobimetinib has since received approval for marketing in New Zealand (Medsafe NZ 2017) for the treatment of patients with melanoma.
FDA approval was based on results from the Phase III CoBRIM study, which showed cobimetinib, when used in combination with vemurafenib, reduced the risk of disease worsening or death by about half in patients with melanoma.
CoBRIM was an international, randomized, double-blind, placebo-controlled phase III study that evaluated the safety and efficacy of 60 mg of cobimetinib once daily plus 960 mg twice daily of vemurafenib compared to 960 mg of vemurafenib twice daily plus placebo. 495 patients were involved in the study, all of whom had previously untreated BRAF V600 mutation-positive, unresectable, locally advanced or metastatic melanoma.
The presence of BRAF V600 mutation was detected using the cobas® 407 4800 BRAF V600 mutation test.
Efficacy results are summarised in Table 1.
The most common (≥ 20%) adverse reactions with cobimetinib were:
Because clinical trials are conducted under widely varying conditions, adverse reaction rates observed in the clinical trials may not reflect the rates observed in practice. In the CoBRIM study, 15% of patients receiving cobimetinib experienced an adverse reaction that resulted in permanent drug discontinuation.
The most common adverse reactions resulting in permanent drug discontinuation were:
Among the 247 patients receiving cobimetinib, adverse reactions led to dose interruption or reductions in 55%. The most common reasons for dose interruptions or reductions of cobimetinib were:
Reporting suspected adverse reactions after authorisation of the medicine is important, as it allows continued monitoring of the benefit/risk balance of the medicine. Healthcare professionals in NZ are advised to report any suspected adverse reactions to the NZ Pharmacovigilance Centre.
There is no experience with overdosage in human clinical trials. In case of suspected overdose, cobimetinib should be withheld and supportive care instituted. There is no specific antidote for overdosage with cobimetinib.
The New Zealand National Poisons Centre on 0800 764 766 should be contacted for advice on the management of overdose.
New Zealand approved datasheets are the official source of information for these prescription medicines, including approved uses and risk information. Check the individual New Zealand datasheet on the Medsafe website.
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