title: One-year and long-term molecular response to nilotinib and dasatinib for newly diagnosed chronic myeloid leukemia: a matching-adjusted indirect comparison.
abstract: BACKGROUND
  Nilotinib and dasatinib have shown superior rates of molecular response (MR) compared to imatinib for the treatment of newly diagnosed chronic myeloid leukemia (CML) in chronic phase (CP). This study indirectly compares MR in patients taking nilotinib 300 mg bid with that in those taking dasatinib 100 mg qd by 12 months and through 48 months.
  
  
  METHODS
  Patients in ENESTnd were re-weighted to match published baseline characteristics reported for DASISION using a propensity score model. After matching, differences in rates of major MR (MMR, measured as a 3 log reduction on the International Scale [IS]), MR(4.0) (4 log reduction on IS), and MR(4.5) (4.5 log reduction on IS) relative to imatinib were indirectly compared between nilotinib and dasatinib. Hazard ratios (HRs) were used to indirectly compare MR outcomes between nilotinib and dasatinib through 48 months of follow-up, while rate differences were used to compare progression to AP/BC between nilotinib and dasatinib by 48 months.
  
  
  RESULTS
  After matching, rates of MR by 12 months were higher with nilotinib vs dasatinib by 11.7% for MMR (p = 0.045), 8.2% for MR(4.0) (p = 0.029), and 8.5% for MR(4.5) (p < 0.001). Higher rates of MMR (HR = 1.44, p = 0.018) and MR(4.0) (HR = 1.58, p = 0.013) achievement were maintained with nilotinib compared to dasatinib through 48 months of follow-up. No statistically significant differences were observed for MR(4.5) through 48 months or progression to AP/BC by 48 months.
  
  
  CONCLUSIONS
  LIMITATIONS include comparisons based solely on indirect evidence and HRs for MR(4.0) and MR(4.5) from the DASISION trial being extracted from cumulative incidence curves.
  
  
  CONCLUSIONS
  This indirect comparison suggests that nilotinib is associated with higher rates of achieving MMR, MR(4.0), and MR(4.5) by 12 months compared to dasatinib for the treatment of newly diagnosed CML-CP. In addition, higher rates of MR achievement with nilotinib were also maintained through 48 months of follow-up.
authors.affiliation: Analysis Group Inc. , Boston, MA , USA.
authors.forename: James E
authors.initials: JE
authors.lastname: Signorovitch
authors.forename: Keith A
authors.initials: KA
authors.lastname: Betts
authors.forename: William M
authors.initials: WM
authors.lastname: Reichmann
authors.forename: Darren
authors.initials: D
authors.lastname: Thomason
authors.forename: Phil
authors.initials: P
authors.lastname: Galebach
authors.forename: Eric Q
authors.initials: EQ
authors.lastname: Wu
authors.forename: Lei
authors.initials: L
authors.lastname: Chen
authors.forename: Daniel J
authors.initials: DJ
authors.lastname: DeAngelo
mesh_terms: D000368:Aged; D000970:Antineoplastic Agents / Q000493:pharmacokinetics / Q000627:therapeutic use; D000069439:Dasatinib; D018450:Disease Progression; D005260:Female; D006801:Humans; D015466:Leukemia, Myeloid, Chronic-Phase / Q000175:diagnosis / Q000188:drug therapy; D008297:Male; D008875:Middle Aged; D058990:Molecular Targeted Therapy / Q000379:methods*; D057216:Propensity Score; D011505:Protein-Tyrosine Kinases / Q000037:antagonists & inhibitors; D011743:Pyrimidines / Q000493:pharmacokinetics / Q000627:therapeutic use; D013844:Thiazoles / Q000493:pharmacokinetics / Q000627:therapeutic use; D016896:Treatment Outcome
chemical_list: D000970:Antineoplastic Agents; D011743:Pyrimidines; D013844:Thiazoles; D011505:Protein-Tyrosine Kinases; C498826:nilotinib; D000069439:Dasatinib
keywords: Chronic myeloid leukemia; Dasatinib; Indirect comparison; Long-term molecular response; Nilotinib