title: Cobimetinib and vemurafenib for the treatment of melanoma.
abstract: BACKGROUND
  Cobimetinib combined with vemurafenib is a new approved MEK inhibitor for first line treatment of metastatic melanoma patients with BRAF V600 mutations. It improves tumor response rates and progression free survival compared to vemurafenib alone, while decreasing toxicities due to the paradoxical activation of the MAPK signaling pathway.
  
  
  METHODS
  This review covers the pharmacology, efficacy, and toxicity data derived from clinical and preclinical studies on cobimetinib. It also reports ongoing trials evaluating cobimetinib to better understand future developments for this drug.
  
  
  CONCLUSIONS
  The combination of cobimetinib and vemurafenib seems to be more toxic than the combination therapy dabrafenib and trametinib even if these four drugs have never been compared in a randomized trial. The future of this combination depends on its capacity to be combined simultaneously or sequentially with immune based therapies to improve the durability of responses.
authors.affiliation: a Dermatology Unit , Hospices Civils de Lyon , Lyon , France.|b INSERM U1052 , Cancer Research Center of Lyon , Lyon , France.|c CNRS UMR 5286 , Cancer Research Center of Lyon , Lyon , France.|d Université Lyon1 , Department of Medecine , Lyon , France.
authors.forename: Amélie
authors.initials: A
authors.lastname: Boespflug
authors.affiliation: a Dermatology Unit , Hospices Civils de Lyon , Lyon , France.|b INSERM U1052 , Cancer Research Center of Lyon , Lyon , France.|c CNRS UMR 5286 , Cancer Research Center of Lyon , Lyon , France.|d Université Lyon1 , Department of Medecine , Lyon , France.
authors.forename: Luc
authors.initials: L
authors.lastname: Thomas
mesh_terms: D000971:Antineoplastic Combined Chemotherapy Protocols / Q000493:pharmacokinetics / Q000494:pharmacology / Q000627:therapeutic use*; D001384:Azetidines / Q000008:administration & dosage; D017321:Clinical Trials, Phase I as Topic; D017322:Clinical Trials, Phase II as Topic; D017326:Clinical Trials, Phase III as Topic; D018572:Disease-Free Survival; D006801:Humans; D007211:Indoles / Q000008:administration & dosage; D048369:MAP Kinase Kinase 1 / Q000037:antagonists & inhibitors; D048370:MAP Kinase Kinase 2 / Q000037:antagonists & inhibitors; D008545:Melanoma / Q000188:drug therapy* / Q000235:genetics; D009154:Mutation; D010880:Piperidines / Q000008:administration & dosage; D048493:Proto-Oncogene Proteins B-raf / Q000235:genetics; D012878:Skin Neoplasms / Q000188:drug therapy* / Q000235:genetics; D013449:Sulfonamides / Q000008:administration & dosage; D000077484:Vemurafenib
chemical_list: D001384:Azetidines; D007211:Indoles; D010880:Piperidines; D013449:Sulfonamides; D000077484:Vemurafenib; C482128:MAP2K2 protein, human; D048493:Proto-Oncogene Proteins B-raf; D048369:MAP Kinase Kinase 1; D048370:MAP Kinase Kinase 2; C482125:MAP2K1 protein, human; C574276:cobimetinib
keywords: BRAF inhibitor; GDC-0973; MEK inhibitor; XL518; cobimetinib; combination therapy; melanoma; vemurafenib