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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.
Limitations:
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.
Conclusion:
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.
Transparency
Declaration of funding
Research was funded by Novartis Pharmaceuticals Corporation, East Hanover, NJ, USA.
Author contributions
All authors participated in the design of the study. J.E.S., E.Q.W., K.A.B., K.P. and E.K. conducted analyses. J.E.S., E.Q.W., K.A.B., K.P., E.K., L.J.W., and D.J.D. have interpreted results. All authors contributed to manuscript development.
Declaration of financial/other interests
J.E.S., E.Q.W., K.A.B., K.P. and E.K. have disclosed that they are employees of Analysis Group, Inc., a company that received funding from Novartis Pharmaceuticals Corporation to conduct this study. A.G., V.K.B. and D.W. have disclosed that they are employees of Novartis Pharmaceuticals Corporation. D.J.D. is a member of a scientific advisory board with Novartis. L.J.W. is on various Data Monitoring Boards for Novartis clinical studies and is a statistical consultant for Novartis. He is also a consultant for Merck, J&J, GSK, Amgen, Roche, Pfizer, Alkermes and Genzyme.
CMRO peer reviewers may have received honoraria for their review work. The peer reviewers on this manuscript have disclosed that they have no relevant financial relationships.