title: Comparative efficacy of nilotinib and dasatinib in newly diagnosed chronic myeloid leukemia: a matching-adjusted indirect comparison of randomized trials.
abstract: OBJECTIVE
  Nilotinib and dasatinib have not been directly compared in a randomized trial for the treatment of newly diagnosed chronic myeloid leukemia in the chronic phase (CML-CP). The purpose of this study was to indirectly compare rates of major molecular response (MMR), progression-free survival (PFS) and overall survival by month 12 with nilotinib and dasatinib treatment of newly diagnosed CML-CP.
  
  
  METHODS
  Individual patient data from a randomized trial of nilotinib vs. imatinib (ENESTnd) and published summary data from a separate randomized trial of dasatinib vs. imatinib (DASISION) were utilized. A matching-adjusted indirect comparison was conducted by weighting individual patients treated with nilotinib to match baseline characteristics reported for dasatinib-treated patients, including age, gender, ECOG performance status and hematology lab values. After matching, efficacy outcomes were compared for patients treated with nilotinib 300 mg twice daily vs. dasatinib 100 mg once daily. Patients randomized to imatinib 400 mg once daily in each trial were used to assess the adequacy of the matching.
  
  
  RESULTS
  Before matching, patients randomized to nilotinib in ENESTnd (n = 273) were older, with a lower median platelet count and more favorable performance status compared to patients randomized to dasatinib in DASISION (n = 259). After matching, all baseline characteristics were balanced across treatment groups. Matched patients treated with nilotinib vs. dasatinib experienced significantly higher rates of MMR (56.8 vs. 45.9%, p = 0.014) and overall survival (99.5 vs. 97.3%, p = 0.046) and numerically higher rates of PFS (98.8 vs. 96.5%). Matched imatinib arms showed no statistically significant or clinically meaningful differences in these outcomes.
  
  
  CONCLUSIONS
  Baseline measures unavailable in one or both trials could not be matched. Adverse event rates were not formally compared across trials due to differences in reporting.
  
  
  CONCLUSIONS
  Nilotinib was associated with significantly higher rates of MMR and overall survival compared with dasatinib by month 12 in the treatment of newly diagnosed CML-CP.
authors.affiliation: Analysis Group , Boston, MA 02199, USA. jsignorovitch@analysisgroup.com
authors.forename: James E
authors.initials: JE
authors.lastname: Signorovitch
authors.forename: Eric Q
authors.initials: EQ
authors.lastname: Wu
authors.forename: Keith A
authors.initials: KA
authors.lastname: Betts
authors.forename: Kejal
authors.initials: K
authors.lastname: Parikh
authors.forename: Evan
authors.initials: E
authors.lastname: Kantor
authors.forename: Amy
authors.initials: A
authors.lastname: Guo
authors.forename: Vamsi K
authors.initials: VK
authors.lastname: Bollu
authors.forename: Denise
authors.initials: D
authors.lastname: Williams
authors.forename: L J
authors.initials: LJ
authors.lastname: Wei
authors.forename: Daniel J
authors.initials: DJ
authors.lastname: DeAngelo
mesh_terms: D000368:Aged; D000970:Antineoplastic Agents / Q000627:therapeutic use*; D000069439:Dasatinib; D005260:Female; D006801:Humans; D015464:Leukemia, Myelogenous, Chronic, BCR-ABL Positive / Q000188:drug therapy*; D008297:Male; D011505:Protein-Tyrosine Kinases / Q000037:antagonists & inhibitors*; D011743:Pyrimidines / Q000627:therapeutic use*; D013844:Thiazoles / Q000627:therapeutic use*; D016896:Treatment Outcome
chemical_list: D000970:Antineoplastic Agents; D011743:Pyrimidines; D013844:Thiazoles; D011505:Protein-Tyrosine Kinases; C498826:nilotinib; D000069439:Dasatinib