title: The relative clinical efficacy of trametinib-dabrafenib and cobimetinib-vemurafenib in advanced melanoma: an indirect comparison.
abstract: OBJECTIVE
  Melanoma causes the majority of skin cancer-related deaths. The outcome of melanoma depends on its stage at diagnosis. Currently, for patients with advanced melanoma, two MEK inhibitors (trametinib and cobimetinib) have been authorized by the European Medicines Agency. The main objective of this study was to compare the relative efficacy of trametinib-dabrafenib and cobimetinib-vemurafenib in patients with advanced melanoma through adjusted indirect treatment comparisons (ITCs).
  
  
  METHODS
  A search was made up to the 3rd of November 2015. Databases consulted were MEDLINE, the Cochrane Library and the Centre for Reviews and Dissemination. Randomized controlled trials (RCTs) which compared the efficacy of trametinib-dabrafenib or cobimetinib-vemurafenib versus a common treatment comparator, in which outcomes of overall survival, progression-free survival (PFS) and overall response rate (ORR) were considered. ITCs were carried out using the method proposed by Bucher et al.
  
  
  CONCLUSIONS
  Two RCTs were included (one for each drugs combination). The results of the adjusted ITCs showed that there were no statistically significant differences between the two combinations in terms of PFS and ORR.
  
  
  CONCLUSIONS
  The ITCs indicate no difference in efficacy between both treatments. However, there should be an independent, head-to-head trial of both combinations to confirm the results.
authors.affiliation: Andalusian Agency for Health Technology Assessment, Seville, Spain.
authors.forename: M
authors.initials: M
authors.lastname: Galván-Banqueri
authors.affiliation: Andalusian Agency for Health Technology Assessment, Seville, Spain.
authors.forename: R
authors.initials: R
authors.lastname: Ubago-Pérez
authors.affiliation: Andalusian Agency for Health Technology Assessment, Seville, Spain.
authors.forename: T
authors.initials: T
authors.lastname: Molina-López
mesh_terms: D000971:Antineoplastic Combined Chemotherapy Protocols / Q000494:pharmacology / Q000627:therapeutic use*; D001384:Azetidines / Q000008:administration & dosage; D018572:Disease-Free Survival; D006801:Humans; D007093:Imidazoles / Q000008:administration & dosage; D007211:Indoles / Q000008:administration & dosage; D008545:Melanoma / Q000188:drug therapy* / Q000473:pathology; D009367:Neoplasm Staging; D010091:Oximes / Q000008:administration & dosage; D010880:Piperidines / Q000008:administration & dosage; D011728:Pyridones / Q000008:administration & dosage; D011744:Pyrimidinones / Q000008:administration & dosage; D016032:Randomized Controlled Trials as Topic; D012878:Skin Neoplasms / Q000188:drug therapy* / Q000473:pathology; D013449:Sulfonamides / Q000008:administration & dosage; D015996:Survival Rate; D016896:Treatment Outcome; D000077484:Vemurafenib
chemical_list: D001384:Azetidines; D007093:Imidazoles; D007211:Indoles; D010091:Oximes; D010880:Piperidines; D011728:Pyridones; D011744:Pyrimidinones; D013449:Sulfonamides; D000077484:Vemurafenib; C560077:trametinib; C574276:cobimetinib; C561627:dabrafenib
keywords: cobimetinib; dabrafenib; indirect treatment comparison; melanoma; trametinib; vemurafenib