title: Cobimetinib.
abstract: OBJECTIVE
  To review and summarize data on cobimetinib, which was approved by the US Food and Drug Administration (FDA) in November 2015 for use in combination with vemurafenib for unresectable or metastatic melanoma with a BRAFV600E or V600K mutation.
  
  
  METHODS
  A literature search using PubMed was conducted using the terms cobimetinib, MEK inhibitor, and melanoma from January 2000 to June 2016.
  
  
  METHODS
  The literature search was confined to human studies published in English. Trials of cobimetinib for melanoma were prioritized.
  
  
  RESULTS
  Cobimetinib is a reversible inhibitor of MEK1 and MEK2. Its FDA approval was based on a phase III, randomized trial of vemurafenib monotherapy (n = 248) or vemurafenib and cobimetinib (n = 247) in unresectable stage IIIC or IV melanoma with a BRAFV600 mutation. Cobimetinib was administered as 60 mg orally daily for 21 days/7 days off, whereas vemurafenib was administered as 960 mg twice daily. Vemurafenib and cobimetinib were associated with an objective response rate of 68%, and median progression-free survival of 9.9 months. The overall survival was not reached at the time of first interim analysis. Clinically relevant grade ≥3 adverse events were diarrhea (6%), rash (6%), photosensitivity (2%), elevated liver function tests (LFTs) (8%-12%), increased creatine kinase (11%), and retinal detachment (3%).
  
  
  CONCLUSIONS
  Cobimetinib combined with vemurafenib is an alternative BRAF/MEK inhibitor therapy for unresectable or metastatic melanoma with BRAFV600 mutation. The role of cobimetinib in melanoma and other solid tumors is likely to expand as the results from ongoing studies become available.
authors.affiliation: 1 Nebraska Medical Center, Omaha, NE, USA.
authors.forename: Jessie
authors.initials: J
authors.lastname: Signorelli
authors.affiliation: 2 Augusta University Medical Center, Augusta, GA, USA.
authors.forename: Arpita
authors.initials: A
authors.lastname: Shah Gandhi
mesh_terms: D000971:Antineoplastic Combined Chemotherapy Protocols / Q000008:administration & dosage / Q000493:pharmacokinetics / Q000627:therapeutic use*; D001384:Azetidines / Q000008:administration & dosage / Q000493:pharmacokinetics / Q000627:therapeutic use*; D002986:Clinical Trials as Topic; D018572:Disease-Free Survival; D006801:Humans; D007211:Indoles / Q000008:administration & dosage / Q000493:pharmacokinetics / Q000627:therapeutic use*; D008545:Melanoma / Q000188:drug therapy* / Q000235:genetics / Q000473:pathology; D009154:Mutation; D010880:Piperidines / Q000008:administration & dosage / Q000493:pharmacokinetics / Q000627:therapeutic use*; D047428:Protein Kinase Inhibitors / Q000627:therapeutic use; D048493:Proto-Oncogene Proteins B-raf / Q000037:antagonists & inhibitors / Q000235:genetics; D013449:Sulfonamides / Q000008:administration & dosage / Q000493:pharmacokinetics / Q000627:therapeutic use*; D014481:United States; D014486:United States Food and Drug Administration; D000077484:Vemurafenib
chemical_list: D001384:Azetidines; D007211:Indoles; D010880:Piperidines; D047428:Protein Kinase Inhibitors; D013449:Sulfonamides; D000077484:Vemurafenib; D048493:Proto-Oncogene Proteins B-raf; C574276:cobimetinib
keywords: cancer; drug development and approval; oncology; pharmacodynamics; pharmacokinetics