title: Panobinostat Plus Bortezomib Versus Lenalidomide in Patients with Relapsed and/or Refractory Multiple Myeloma: A Matching-Adjusted Indirect Treatment Comparison of Survival Outcomes using Patient-level Data.
abstract: BACKGROUND
  In the UK, the standard of care for patients with multiple myeloma who received ≥2 prior treatments is lenalidomide plus dexamethasone (LEN + DEX) and pomalidomide plus DEX (POM + DEX) (in Wales only). Recently, panobinostat plus bortezomib and DEX (PAN + BTZ + DEX) was licensed in this setting. The current study assessed the progression-free survival (PFS) and overall survival (OS) outcomes with PAN + BTZ + DEX versus LEN + DEX (primary comparator) and POM + DEX (exploratory comparator).
  
  
  METHODS
  Since an anchor-based indirect treatment comparison was not feasible, the matching-adjusted indirect treatment comparison approach was used. To compare the survival outcomes, patient-level data were generated for the comparators utilizing published Kaplan-Meier survival estimates. The use of approximated patient-level data and matched data for PAN + BTZ + DEX allowed the use of Cox proportional hazards models and the assessment of the proportional hazards assumption. In cases where there was evidence that the proportional hazards assumption was violated, time-dependent hazard ratios (HRs) were estimated. Median and mean values for PFS and OS were predicted.
  
  
  RESULTS
  For both PFS and OS, the proportional hazards assumption was not satisfied, therefore time-dependent HRs were estimated. Using time-dependent HRs, the mean PFS was estimated to be 11.83 months for PAN + BTZ + DEX and 10.96 months for LEN + DEX. The corresponding mean OS estimates were 30.73 and 27.76 months, respectively. Comparisons with POM + DEX were affected by large uncertainty and did not allow making robust inferences.
  
  
  CONCLUSIONS
  To our knowledge, this is the first study that combined matching-adjusted indirect treatment comparison with time-dependent HRs to address changing patterns in the HR. The results suggest that treatment with PAN + BTZ + DEX and LEN + DEX are associated with similar mean PFS and OS in the third-line treatment setting of multiple myeloma.
authors.affiliation: Pharmerit International, Health Economics and Outcomes Research, Marten Meesweg 107, 3068 AV, Rotterdam, The Netherlands.
authors.forename: Istvan
authors.initials: I
authors.lastname: Majer
authors.affiliation: Pharmerit International, Health Economics and Outcomes Research, Marten Meesweg 107, 3068 AV, Rotterdam, The Netherlands. gvandewetering@pharmerit.com.
authors.forename: Gijs
authors.initials: G
authors.lastname: van de Wetering
authors.affiliation: Novartis Pharmaceuticals UK, Surrey, UK.
authors.forename: Zoltan
authors.initials: Z
authors.lastname: Polanyi
authors.affiliation: Novartis Pharmaceuticals UK, Surrey, UK.
authors.forename: Arun
authors.initials: A
authors.lastname: Krishna
authors.affiliation: Novartis Pharmaceuticals UK, Surrey, UK.
authors.forename: Elisabeth
authors.initials: E
authors.lastname: Gray
authors.affiliation: Novartis Pharmaceuticals Corporation, East Hanover, NJ, USA.
authors.forename: Anuja
authors.initials: A
authors.lastname: Roy
mesh_terms: D000970:Antineoplastic Agents / Q000008:administration & dosage / Q000627:therapeutic use*; D000069286:Bortezomib / Q000008:administration & dosage / Q000627:therapeutic use*; D004359:Drug Therapy, Combination; D005260:Female; D006801:Humans; D006877:Hydroxamic Acids / Q000008:administration & dosage / Q000627:therapeutic use*; D007211:Indoles / Q000008:administration & dosage / Q000627:therapeutic use*; D053208:Kaplan-Meier Estimate; D000077269:Lenalidomide; D008297:Male; D008875:Middle Aged; D009101:Multiple Myeloma / Q000188:drug therapy* / Q000401:mortality; D000077767:Panobinostat; D016016:Proportional Hazards Models; D012008:Recurrence; D016019:Survival Analysis; D013792:Thalidomide / Q000031:analogs & derivatives* / Q000627:therapeutic use; D016896:Treatment Outcome
chemical_list: D000970:Antineoplastic Agents; D006877:Hydroxamic Acids; D007211:Indoles; D013792:Thalidomide; D000069286:Bortezomib; D000077767:Panobinostat; D000077269:Lenalidomide