title: Dabrafenib in an elderly patient with metastatic melanoma and BRAF V600R mutation: a case report.
abstract: BACKGROUND
  Approximately 50 % of malignant melanomas harbor activating point mutations in the BRAF gene. Typically, these mutations result in the substitution of the amino acid valine at codon 600 of the gene, and 90-95 % of mutations are either BRAF (V600E) or BRAF (V600K). Specific BRAF inhibitors such as dabrafenib and vemurafenib are the mainstays of treatment in patients with metastatic BRAF-mutant malignant melanomas. The third most common BRAF mutation is V600R, which also leads to increased BRAF signaling. Although evidence exists about the activity of dabrafenib and vemurafenib in patients with the BRAF (V600R) mutation, these patients have been systematically excluded from recent trials with targeted therapies.
  
  
  METHODS
  Here, we report the positive results in terms of survival and quality of life obtained with dabrafenib in an 80-year-old Caucasian male patient with a Charlson Comorbidity Index of 8 diagnosed with metastatic malignant melanoma harboring the BRAF (V600R) mutation. Our patient was treated with dabrafenib for 7 months with minimal toxicity. We also report exploratory analyses of circulating tumor DNA during targeted treatment. Interestingly, the mutation was not detected after starting treatment and became detectable before radiological disease progression.
  
  
  CONCLUSIONS
  Our report suggests that (1) a relevant benefit can be obtained with a BRAF inhibitor in real-world patients with a malignant melanoma harboring a BRAF (V600R) mutation, and that (2) circulating tumor DNA detection might be of help in assessing tumor burden in everyday clinical practice. The results reported here should encourage the inclusion of patients with BRAF (V600R)-mutated malignant melanomas in future prospective clinical trials with BRAF inhibitors.
authors.affiliation: Medical Oncology Department, Hospital del Mar, Passeig Marítim 25-29, 08003, Barcelona, Spain. dcasadevall@parcdesalutmar.cat.|Cancer Research Program, IMIM (Hospital del Mar Medical Research Institute), Barcelona, Spain. dcasadevall@parcdesalutmar.cat.
authors.forename: David
authors.initials: D
authors.lastname: Casadevall
authors.affiliation: Medical Oncology Department, Hospital del Mar, Passeig Marítim 25-29, 08003, Barcelona, Spain.|Cancer Research Program, IMIM (Hospital del Mar Medical Research Institute), Barcelona, Spain.
authors.forename: Joana
authors.initials: J
authors.lastname: Vidal
authors.affiliation: Dermatology Department, Hospital del Mar, Barcelona, Spain.
authors.forename: Fernando
authors.initials: F
authors.lastname: Gallardo
authors.affiliation: Radiology Department, Hospital del Mar, Barcelona, Spain.
authors.forename: Flavio
authors.initials: F
authors.lastname: Zuccarino
authors.affiliation: Pathology Department, Hospital del Mar, Barcelona, Spain.|Cancer Research Program, IMIM (Hospital del Mar Medical Research Institute), Barcelona, Spain.
authors.forename: Montserrat
authors.initials: M
authors.lastname: Arumí-Uría
authors.affiliation: Pathology Department, Hospital del Mar, Barcelona, Spain.|Cancer Research Program, IMIM (Hospital del Mar Medical Research Institute), Barcelona, Spain.
authors.forename: Alba
authors.initials: A
authors.lastname: Dalmases
authors.affiliation: Pathology Department, Hospital del Mar, Barcelona, Spain.|Cancer Research Program, IMIM (Hospital del Mar Medical Research Institute), Barcelona, Spain.
authors.forename: Beatriz
authors.initials: B
authors.lastname: Bellosillo
authors.affiliation: Medical Oncology Department, Hospital del Mar, Passeig Marítim 25-29, 08003, Barcelona, Spain.|Cancer Research Program, IMIM (Hospital del Mar Medical Research Institute), Barcelona, Spain.
authors.forename: Clara
authors.initials: C
authors.lastname: Montagut
mesh_terms: D000369:Aged, 80 and over; D000970:Antineoplastic Agents / Q000627:therapeutic use*; D001932:Brain Neoplasms / Q000000981:diagnostic imaging / Q000556:secondary; D004428:Ear Neoplasms / Q000188:drug therapy* / Q000235:genetics / Q000473:pathology; D006801:Humans; D007093:Imidazoles / Q000627:therapeutic use*; D008113:Liver Neoplasms / Q000000981:diagnostic imaging / Q000188:drug therapy* / Q000556:secondary; D008175:Lung Neoplasms / Q000000981:diagnostic imaging / Q000188:drug therapy* / Q000556:secondary; D008279:Magnetic Resonance Imaging; D008297:Male; D008545:Melanoma / Q000000981:diagnostic imaging / Q000188:drug therapy* / Q000235:genetics / Q000556:secondary; D009154:Mutation; D010091:Oximes / Q000627:therapeutic use*; D048493:Proto-Oncogene Proteins B-raf / Q000235:genetics; D011788:Quality of Life; D012878:Skin Neoplasms / Q000188:drug therapy* / Q000235:genetics / Q000473:pathology; D014057:Tomography, X-Ray Computed; D016896:Treatment Outcome
chemical_list: D000970:Antineoplastic Agents; D007093:Imidazoles; D010091:Oximes; C482119:BRAF protein, human; D048493:Proto-Oncogene Proteins B-raf; C561627:dabrafenib
keywords: BRAF; Dabrafenib; Melanoma; V600R; ctDNA