A propensity score matching analysis of dasatinib and nilotinib as a frontline therapy for patients with chronic myeloid leukemia in chronic phase

Abstract

Background Both dasatinib and nilotinib are approved frontline therapy for chronic myeloid leukemia, chronic phase (CML-CP) based on randomized trials compared to imatinib. However, no head to head comparison of dasatinib and nilotinib has been conducted in newly diagnosed CML-CP patients. Method We conducted a propensity score (PS) matched comparison of patients with CML-CP, who received front-line therapy by either dasatinib (N = 102) or nilotinib (N = 104) under the respective phase II trials conducted in parallel. Result PS matching resulted in 87 patients from each trial to be matched for pre-treatment characteristics. The 3-month BCR-ABL1/ABL1 <10% rate was 93% with dasatinib and 94% with nilotinib (p=0.25), respectively. Rates of major molecular response (MMR) at 12 months were 77% and 85% (p=0.13), respectively, and MR4.5 at 36 months are 66% and 64% (p=0.96), respectively. All other clinically relevant response were similar between the two treatment cohorts. The 3-year probability of event-free survival was 89% in the dasatinib-treated patients and 87% for those treated with nilotinib (p=0.99). Corresponding 3-year overall survival probabilities were 99% and 93%, respectively (p=0.95). No statistical difference was observed between dasatinib and nilotinib treated groups in any of the other survival endpoints. Treatment discontinuation rate was also similar between the two cohorts (18% in dasatinib and 19% in nilotinib, P = 0.82). Conclusion In PS matched cohort of newly diagnosed CML-CP patients, dasatinib and nilotinib offer similar response and survival outcomes. Both drugs can be considered as reasonable standard of care options as a first line therapy in CML-CP patients.

Excellent outcomes of 2G-TKI therapy after imatinib failure in chronic phase CML patients

“…Second generation TKIs have never been compared head-to-head in a prospective clinical trial, neither in the first- nor in the second-line setting, and a comparison of the results reported in the phase 2 studies that led to drugs’ registration are difficult because of different patient selection and protocol criteria [ 10 ]. A propensity score matching analysis in the front-line setting demonstrated that DAS and NIL offer similar response rates and survival outcomes [ 11 ]. Besides a few cost-effective analyses on second-line treatments after IM failure [ 12 – 14 ], the only experience focused on a comparison between DAS and NIL on clinical outcomes in IM-resistant or intolerant patients came from an online medical chart review of 597 CML patients treated by 122 haematologists and oncologists in the United States [ 15 ].…”

Tyrosine kinase inhibitors (TKIs) used in the management of chronic myeloid leukaemia are associated with haematologic toxicities—Which TKI is the safest?

“…In another study, the authors conducted a propensity score matched comparison of patients with CML-CP who received frontline therapy with either dasatinib (n = 107; 100 mg/ day) or nilotinib (n = 104; 800 mg/day) from two single-arm, singleinstitution phase II trials. 13 Besides showing similar response and survival outcomes, frontline dasatinib and nilotinib therapies were comparable regarding all grade ≥III haematologic toxicities (anaemia, neutropenia, and thrombocytopenia).…”

First-line therapy for chronic phase CML: selecting the optimal BCR-ABL1-targeted TKI

“…Overall, despite differences in molecular responses comparing dasatinib or nilotinib with imatinib, the OS rates across these agents are not statistically significantly different [8][9][10]. Further, propensity score matching of 87 dasatinib-or nilotinib-treated patients reported no major differences in response or survival endpoints [29]. One factor confounding analysis of outcomes for the treatment of CML is that many deaths occur from causes unrelated to CML [8][9][10].…”