Artikel
Choosing a Tyrosine Kinase Inhibitor as First-line Therapy for Chronic Myeloid Leukemia under the Uncertainty of Long-term Effectiveness and Safety
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Veröffentlicht: | 11. März 2013 |
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Gliederung
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Background: The introduction of the tyrosine kinase inhibitor (TKI) imatinib about a decade ago dramatically extended the life span of chronic myeloid leukemia (CML) patients. Currently, there are several different TKIs approved for CML treatment. Long-term effectiveness and safety data for second-generation TKIs are not yet available. Despite this uncertainty about long-term effects, patients and physicians have to choose a first-line therapy. The aim of our study is to develop a clinical decision-analytic model to extrapolate short-term outcomes and to evaluate the comparative long-term effectiveness of first-line therapy for CML within the Austrian health care context.
Methods: We developed a Markov state-transition model for patients in the chronic-phase of CML treated with first-line TKI imatinib, dasatinib or nilotinib. Seven different strategies including different combinations of first and second-generation TKIs as well as chemotherapy or stem cell transplantation were evaluated. The model was parameterized using published trial data, data from the Austrian CML registry and from an Austrian CML expert panel [1], [2], [3], [4], [5], [6], [7], [8], [9], [10], [11]. The model was analyzed as a cohort simulation over a lifelong time horizon. Health outcomes evaluated were life-years (LYs) gained and quality-adjusted life years (QALYs) gained. Deterministic and structural sensitivity analyses were performed.
Results: Nilotinib followed by dasatinib after failure is the most effective treatment in terms of both LYs gained (19.7 LY) and QALYs gained (17.1 QALYs). All strategies including a second-line TKI were superior compared to strategies without second-line TKI. Deterministic sensitivity analyses showed that the ranking of the strategies was mostly influenced by the duration of first- and second-line therapies. In a structural sensitivity analysis, where patients move directly from second-line TKI therapy to advanced stage of disease, strategies without second-line therapy are most effective.
Conclusions: Based on our analyses results, the most clinically effective strategy is nilotinib followed by dasatinib as second-line therapy. All three TKIs are approved as first-line therapy in Austria. Our results may support clinicians and patients in their decision making.
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