title: The safety and efficacy of cobimetinib for the treatment of BRAF V600E or V600K melanoma.
abstract: BACKGROUND
  In the recent years, melanoma patients' outcome and survival improved, mainly because of systemic treatment improvement with targeted therapy and checkpoint blockade. Targeted therapy with BRAF and MEK inhibitors was approved to treat patients with unresectable or metastatic melanoma, harboring BRAF V600 mutations. This paper addresses the safety and efficacy of cobimetinib, when used in combination with vemurafenib, in the previous mentioned setting.
  
  
  METHODS
  This article presents an overview on the rationale for clinical development of cobimetinib, as well as the mechanism of action, the efficacy and safety, and the most important trials that led to the approval of the combination therapy with vemurafenib. We searched the PubMed for published papers related to safety and efficacy of cobimetinib, and resistance mechanisms to BRAF inhibition. The abstract databases of the American Society of Clinical Oncology and European Society for Medical Oncology were also searched for updates on the mentioned clinical trials. Expert commentary: Patients treated with targeted therapy experience a rapid tumor response. However, virtually all patients will develop resistance to treatment. Therapeutic combinations to overcome resistance mechanisms are currently addressed. In the future, targeted therapy strategy will include three or more drugs, probably from different therapeutic classes.
authors.affiliation: a Center for Dermatooncology, Department of Dermatology , University Hospital Tübingen , Tübingen , Germany.|b Military Health Care Department , Portuguese Air Force Health Direction , Lisbon , Portugal.
authors.forename: Teresa
authors.initials: T
authors.lastname: Amaral
authors.affiliation: a Center for Dermatooncology, Department of Dermatology , University Hospital Tübingen , Tübingen , Germany.
authors.forename: Noura
authors.initials: N
authors.lastname: Nouri
authors.affiliation: a Center for Dermatooncology, Department of Dermatology , University Hospital Tübingen , Tübingen , Germany.
authors.forename: Claus
authors.initials: C
authors.lastname: Garbe
mesh_terms: D000971:Antineoplastic Combined Chemotherapy Protocols / Q000008:administration & dosage / Q000009:adverse effects / Q000494:pharmacology; D001384:Azetidines / Q000008:administration & dosage* / Q000009:adverse effects / Q000494:pharmacology; D019008:Drug Resistance, Neoplasm; D006801:Humans; D007211:Indoles / Q000008:administration & dosage; D008545:Melanoma / Q000188:drug therapy* / Q000235:genetics / Q000473:pathology; D009154:Mutation; D010880:Piperidines / Q000008:administration & dosage* / Q000009:adverse effects / Q000494:pharmacology; D047428:Protein Kinase Inhibitors / Q000008:administration & dosage / Q000009:adverse effects / Q000494:pharmacology; D048493:Proto-Oncogene Proteins B-raf / Q000235:genetics*; D012878:Skin Neoplasms / Q000188:drug therapy / Q000235:genetics / Q000473:pathology; D013449:Sulfonamides / Q000008:administration & dosage; D000077484:Vemurafenib
chemical_list: D001384:Azetidines; D007211:Indoles; D010880:Piperidines; D047428:Protein Kinase Inhibitors; D013449:Sulfonamides; D000077484:Vemurafenib; C482119:BRAF protein, human; D048493:Proto-Oncogene Proteins B-raf; C574276:cobimetinib
keywords: BRAF mutated metastatic melanoma; BRAF mutation; BRAF/MEK inhibition; Cobimetinib; MAPK pathway; combination targeted therapy