title: Successful retreatment with combined BRAF/MEK inhibition in metastatic BRAFV600-mutated melanoma.
abstract: BACKGROUND
  The combination treatment with BRAF and MEK inhibitors is amongst the current standard of care for stage IIIC/IV BRAF-mutated melanoma. However, therapeutic options are limited once patients have progressed upon both targeted and immunotherapy.
  
  
  OBJECTIVE
  To investigate whether retreatment with BRAF and MEK inhibitor combination is an option for patients with metastatic BRAF-mutated melanoma upon previous progression on kinase inhibitors.
  
  
  METHODS
  Two patients with metastatic BRAF-mutated melanoma were rechallenged with BRAF and MEK inhibitor combination after progression on targeted therapy and subsequent immunotherapy with anti-CTLA-4 and anti-PD-1 antibodies.
  
  
  RESULTS
  Both patients responded to retreatment. Responses were limited to a few months and associated with a considerable increase in quality of life.
  
  
  CONCLUSIONS
  Retreatment with BRAF and MEK inhibitors may present a feasible treatment option upon progression on both kinase inhibitors and immunotherapy, and should be considered when all other treatment options have been exhausted.
authors.affiliation: Department of Dermatology, University Hospital Zurich, Zurich, Switzerland.|University Department of Medicine, Kantonsspital Aarau, Aarau, Switzerland.
authors.forename: V C
authors.initials: VC
authors.lastname: Amann
authors.affiliation: Department of Gynecology and Obstetrics, Herrenberg Hospital, Herrenberg, Germany.
authors.forename: D
authors.initials: D
authors.lastname: Hoffmann
authors.affiliation: Department of Dermatology, University Hospital Zurich, Zurich, Switzerland.
authors.forename: J
authors.initials: J
authors.lastname: Mangana
authors.affiliation: Department of Dermatology, University Hospital Zurich, Zurich, Switzerland.
authors.forename: R
authors.initials: R
authors.lastname: Dummer
authors.affiliation: Department of Dermatology, University Hospital Zurich, Zurich, Switzerland.
authors.forename: S M
authors.initials: SM
authors.lastname: Goldinger
mesh_terms: D000970:Antineoplastic Agents / Q000627:therapeutic use*; D005260:Female; D006801:Humans; D020930:MAP Kinase Kinase Kinases / Q000037:antagonists & inhibitors*; D008297:Male; D008545:Melanoma / Q000188:drug therapy* / Q000235:genetics / Q000473:pathology; D008875:Middle Aged; D009362:Neoplasm Metastasis; D047428:Protein Kinase Inhibitors / Q000627:therapeutic use*; D048493:Proto-Oncogene Proteins B-raf / Q000037:antagonists & inhibitors*; D011788:Quality of Life
chemical_list: D000970:Antineoplastic Agents; D047428:Protein Kinase Inhibitors; C482119:BRAF protein, human; D048493:Proto-Oncogene Proteins B-raf; D020930:MAP Kinase Kinase Kinases