title: Vemurafenib for the treatment of locally advanced or metastatic BRAF V600 mutation-positive malignant melanoma: a NICE single technology appraisal.
abstract: Vemurafenib is an oral BRAF inhibitor licenced for the treatment of locally advanced or metastatic BRAF V600-mutation positive malignant melanoma. The manufacturer of vemurafenib, Roche Products Limited, was invited by the National Institute for Health and Care Excellence (NICE) to submit evidence of the drug's clinical- and cost-effectiveness for its licenced indication, to inform the Institute's Single Technology Appraisal (STA) process. The Liverpool Reviews and Implementation Group (LRiG) at the University of Liverpool was commissioned to act as the Evidence Review Group (ERG) for this appraisal. This article summarises the ERG's review of the evidence submitted by the manufacturer and also includes a summary of the NICE Appraisal Committee (AC) decision. The ERG reviewed the clinical- and cost-effectiveness evidence in accordance with the decision problem defined by NICE. The ERG's analysis of the submitted economic model assessed the appropriateness of the approach taken by the manufacturer in modelling the decision problem. It also included an assessment of the reliability of model implementation and the extent of conformity to published standards and prevailing norms of practice within the health economics modelling community. Particular attention was paid to issues likely to impact substantially on the base-case cost-effectiveness results. The clinical evidence was derived from BRIM 3 (BRAF Inhibitor in Melanoma 3), a well-designed, multi-centre, multi-national, phase III, randomised controlled trial (RCT). Clinical outcome results from the October 2011 data cut showed that median overall survival for patients treated with vemurafenib was 13.2 months compared with 9.6 months for those treated with dacarbazine. The ERG's main concern with the trial was the potential for confounding because of the early introduction of the crossover from the comparator drug to vemurafenib or another BRAF inhibitor. The submitted incremental cost-effectiveness ratio (ICER) was considered above the NICE threshold, even when end-of-life criteria were taken into account. The ERG questioned the submitted economic model on a number of grounds, particularly the approach used to project trial results. After the ERG had made appropriate corrections to the model and employed an alternative form of projective modelling, the ICER per quality-adjusted life year more than doubled. Additional evidence was submitted by the manufacturer for consideration at a second AC meeting and at their third meeting the AC concluded that vemurafenib could be recommended as first-line maintenance treatment for patients with locally advanced or metastatic BRAF V600 mutation-positive malignant melanoma.
authors.affiliation: Liverpool Reviews and Implementation Group, University of Liverpool, Whelan Building, Brownlow Hill, Liverpool, L69 3GB, UK, s.beale@liv.ac.uk.
authors.forename: Sophie
authors.initials: S
authors.lastname: Beale
authors.forename: Rumona
authors.initials: R
authors.lastname: Dickson
authors.forename: Adrian
authors.initials: A
authors.lastname: Bagust
authors.forename: Michaela
authors.initials: M
authors.lastname: Blundell
authors.forename: Yenal
authors.initials: Y
authors.lastname: Dundar
authors.forename: Angela
authors.initials: A
authors.lastname: Boland
authors.forename: Ernie
authors.initials: E
authors.lastname: Marshall
authors.forename: Ruth
authors.initials: R
authors.lastname: Plummer
authors.forename: Chris
authors.initials: C
authors.lastname: Proudlove
mesh_terms: D000970:Antineoplastic Agents / Q000008:administration & dosage / Q000191:economics / Q000627:therapeutic use*; D003362:Cost-Benefit Analysis; D004345:Drug Industry / Q000191:economics; D006801:Humans; D007211:Indoles / Q000008:administration & dosage / Q000191:economics / Q000627:therapeutic use*; D008545:Melanoma / Q000188:drug therapy* / Q000201:enzymology / Q000235:genetics; D009154:Mutation; D009361:Neoplasm Invasiveness; D009362:Neoplasm Metastasis; D048493:Proto-Oncogene Proteins B-raf / Q000037:antagonists & inhibitors* / Q000235:genetics; D019057:Quality-Adjusted Life Years; D016032:Randomized Controlled Trials as Topic; D013449:Sulfonamides / Q000008:administration & dosage / Q000191:economics / Q000627:therapeutic use*; D013673:Technology Assessment, Biomedical / Q000191:economics*; D000077484:Vemurafenib
chemical_list: D000970:Antineoplastic Agents; D007211:Indoles; D013449:Sulfonamides; D000077484:Vemurafenib; C482119:BRAF protein, human; D048493:Proto-Oncogene Proteins B-raf