title: Sequential treatment with immunotherapy and BRAF inhibitors in BRAF-mutant advanced melanoma.
abstract: OBJECTIVE
  Immunotherapy (IT) agents and BRAF inhibitors (BRAFi) are effective treatments for patients with advanced BRAF-mutant melanoma although the optimal sequence remains to be elucidated. The aim of this study was to compare the outcomes of two different cohorts of patients treated with BRAFi first, then IT or the reverse sequence.
  
  
  METHODS
  This is a retrospective study on two groups of patients: a cohort was treated first with BRAFi followed by immunotherapy (BRAFi-IT) and the other cohort with the reverse sequence (IT-BRAFi). Baseline characteristics and clinical outcomes were compared between the two cohorts.
  
  
  RESULTS
  A total of 25 patients were included in the study. Sixteen patients were given BRAFi-IT sequence and nine received IT-BRAFi sequence. No differences were observed in the characteristics of patients prior to each treatment between cohorts. Objective response rate (ORR) achieved by BRAFi were not different among groups. ORR achieved by IT was higher when administered after BRAFi (43.8 vs 0 %). Survival rates at 1-2 years were similar in both cohorts and median overall survival was not different for BRAFi-IT and IT-BRAFi (log rank test p = 0.97).
  
  
  CONCLUSIONS
  No differences were observed in OS between the two cohorts. These results support the indistinct use of IT or BRAFi as initial treatment in patients with metastatic BRAF-mutant melanoma, although higher rate of response to IT was observed when administered after BRAFi. Prospective randomized clinical trials are needed on this issue.
authors.affiliation: Department of Medical Oncology, Hospital Clínic, Barcelona, Spain. faya@clinic.ub.es.|Translational Genomics and Targeted Therapeutics in Solid Tumors, Institut d'Investigacions Biomèdiques August Pi i Sunyer (IDIBAPS), Barcelona, Spain. faya@clinic.ub.es.
authors.forename: F
authors.initials: F
authors.lastname: Aya
authors.affiliation: Department of Medical Oncology, Hospital Clínic, Barcelona, Spain.|Translational Genomics and Targeted Therapeutics in Solid Tumors, Institut d'Investigacions Biomèdiques August Pi i Sunyer (IDIBAPS), Barcelona, Spain.
authors.forename: A
authors.initials: A
authors.lastname: Fernandez-Martinez
authors.affiliation: Department of Medical Oncology, Hospital Clínic, Barcelona, Spain.|Translational Genomics and Targeted Therapeutics in Solid Tumors, Institut d'Investigacions Biomèdiques August Pi i Sunyer (IDIBAPS), Barcelona, Spain.
authors.forename: L
authors.initials: L
authors.lastname: Gaba
authors.affiliation: Department of Medical Oncology, Hospital Clínic, Barcelona, Spain.|Translational Genomics and Targeted Therapeutics in Solid Tumors, Institut d'Investigacions Biomèdiques August Pi i Sunyer (IDIBAPS), Barcelona, Spain.
authors.forename: I
authors.initials: I
authors.lastname: Victoria
authors.affiliation: Department of Medical Oncology, Hospital Clínic, Barcelona, Spain.|Translational Genomics and Targeted Therapeutics in Solid Tumors, Institut d'Investigacions Biomèdiques August Pi i Sunyer (IDIBAPS), Barcelona, Spain.
authors.forename: M
authors.initials: M
authors.lastname: Tosca
authors.affiliation: Department of Medical Oncology, Hospital Clínic, Barcelona, Spain.|Translational Genomics and Targeted Therapeutics in Solid Tumors, Institut d'Investigacions Biomèdiques August Pi i Sunyer (IDIBAPS), Barcelona, Spain.
authors.forename: E
authors.initials: E
authors.lastname: Pineda
authors.affiliation: Department of Medical Oncology, Hospital Clínic, Barcelona, Spain.
authors.forename: P
authors.initials: P
authors.lastname: Gascon
authors.affiliation: Department of Medical Oncology, Hospital Clínic, Barcelona, Spain.|Translational Genomics and Targeted Therapeutics in Solid Tumors, Institut d'Investigacions Biomèdiques August Pi i Sunyer (IDIBAPS), Barcelona, Spain.
authors.forename: A
authors.initials: A
authors.lastname: Prat
authors.affiliation: Department of Medical Oncology, Hospital Clínic, Barcelona, Spain.|Translational Genomics and Targeted Therapeutics in Solid Tumors, Institut d'Investigacions Biomèdiques August Pi i Sunyer (IDIBAPS), Barcelona, Spain.
authors.forename: A
authors.initials: A
authors.lastname: Arance
mesh_terms: D000293:Adolescent; D000328:Adult; D000368:Aged; D000369:Aged, 80 and over; D000911:Antibodies, Monoclonal / Q000627:therapeutic use*; D000971:Antineoplastic Combined Chemotherapy Protocols / Q000627:therapeutic use*; D005260:Female; D005500:Follow-Up Studies; D006801:Humans; D007167:Immunotherapy; D008297:Male; D008545:Melanoma / Q000188:drug therapy* / Q000276:immunology / Q000473:pathology; D008875:Middle Aged; D009154:Mutation / Q000235:genetics*; D009367:Neoplasm Staging; D011379:Prognosis; D047428:Protein Kinase Inhibitors / Q000627:therapeutic use*; D048493:Proto-Oncogene Proteins B-raf / Q000037:antagonists & inhibitors* / Q000235:genetics*; D012189:Retrospective Studies; D015996:Survival Rate; D055815:Young Adult
chemical_list: D000911:Antibodies, Monoclonal; D047428:Protein Kinase Inhibitors; C482119:BRAF protein, human; D048493:Proto-Oncogene Proteins B-raf
keywords: BRAF inhibitors; BRAF mutant; Immunotherapy; Melanoma