title: Vemurafenib for BRAF V600 mutated advanced melanoma: results of treatment beyond progression.
abstract: BACKGROUND
  Selective BRAF inhibition (BRAFi) by vemurafenib or dabrafenib has become approved standard treatment in BRAF V600 mutated advanced stage melanoma. While the response rate is high, the response duration is limited with a progression-free survival (PFS) of 5-6months. Our observation of accelerated disease progression within some patients after stopping vemurafenib treatment has fostered the idea of treatment beyond progression (BRAFi TBP).
  
  
  METHODS
  In this retrospective study, we analysed 70 metastatic melanoma patients, treated at our institute, who experienced progression after prior objective response upon treatment with vemurafenib. Thirty-five patients that continued treatment beyond progression are compared with 35 patients who stopped BRAFi treatment at disease progression.
  
  
  RESULTS
  Median overall survival beyond documented progression was found to be 5.2months versus 1.4months (95% confidence interval (CI): 3.8-7.4 versus 0.6-3.4; Log-Rank p=0.002) in favour of BRAFi TBP. In the multivariate survival analysis, stopping treatment at disease progression was significantly associated with shorter survival (hazard ratio: 1.92; 95% CI: 1.04-3.55; p=0.04).
  
  
  CONCLUSIONS
  Our results suggest that continuing vemurafenib treatment beyond progression may be beneficial in advanced melanoma patients, who prior to progression responded to vemurafenib.
authors.affiliation: Division of Medical Oncology, The Netherlands Cancer Institute, Amsterdam, The Netherlands.
authors.forename: A
authors.initials: A
authors.lastname: Scholtens
authors.affiliation: Division of Medical Oncology, The Netherlands Cancer Institute, Amsterdam, The Netherlands.
authors.forename: M H
authors.initials: MH
authors.lastname: Geukes Foppen
authors.affiliation: Division of Medical Oncology, The Netherlands Cancer Institute, Amsterdam, The Netherlands.
authors.forename: C U
authors.initials: CU
authors.lastname: Blank
authors.affiliation: Division of Medical Oncology, The Netherlands Cancer Institute, Amsterdam, The Netherlands.
authors.forename: J V
authors.initials: JV
authors.lastname: van Thienen
authors.affiliation: Division of Medical Oncology, The Netherlands Cancer Institute, Amsterdam, The Netherlands.
authors.forename: H
authors.initials: H
authors.lastname: van Tinteren
authors.affiliation: Division of Medical Oncology, The Netherlands Cancer Institute, Amsterdam, The Netherlands. Electronic address: j.haanen@nki.nl.
authors.forename: J B
authors.initials: JB
authors.lastname: Haanen
mesh_terms: D000328:Adult; D000368:Aged; D018450:Disease Progression; D018572:Disease-Free Survival; D004334:Drug Administration Schedule; D005260:Female; D006801:Humans; D007211:Indoles / Q000008:administration & dosage*; D053208:Kaplan-Meier Estimate; D008297:Male; D008545:Melanoma / Q000188:drug therapy* / Q000201:enzymology / Q000235:genetics / Q000401:mortality / Q000473:pathology; D008875:Middle Aged; D015999:Multivariate Analysis; D009154:Mutation; D009426:Netherlands; D016016:Proportional Hazards Models; D047428:Protein Kinase Inhibitors / Q000008:administration & dosage*; D048493:Proto-Oncogene Proteins B-raf / Q000037:antagonists & inhibitors* / Q000235:genetics* / Q000378:metabolism; D012189:Retrospective Studies; D012307:Risk Factors; D012878:Skin Neoplasms / Q000188:drug therapy* / Q000201:enzymology / Q000235:genetics / Q000401:mortality / Q000473:pathology; D013449:Sulfonamides / Q000008:administration & dosage*; D013997:Time Factors; D016896:Treatment Outcome; D000077484:Vemurafenib
chemical_list: D007211:Indoles; D047428:Protein Kinase Inhibitors; D013449:Sulfonamides; D000077484:Vemurafenib; C482119:BRAF protein, human; D048493:Proto-Oncogene Proteins B-raf
keywords: BRAF inhibitor; Cutaneous melanoma; Overall survival; Treatment beyond progression; Vemurafenib