San Francisco, CA—Once Gleevec loses patent exclusivity in 2016, imatinib will become the most cost-effective initial treatment strategy for patients with newly diagnosed chronic myeloid leukemia (CML) in chronic phase, said Richard A. Larson, MD, Director, Hematologic Malignancies Clinical Research Program, University of Chicago, IL, at ASH 2014.
Dr Larson’s analysis showed an incremental cost-effectiveness ratio of $291,000 per quality-adjusted life-year (QALY) when generic imatinib was used as the initial therapy in a step therapy regimen.
Lifelong treatment with a tyrosine kinase inhibitor (TKI) is recommended for patients with chronic-phase CML, and although out-of-pocket costs vary within and between health systems, they may be considerable, and costs influence daily adherence and outcomes, Dr Larson said.
Currently, imatinib, dasatinib, and nilotinib are approved by the FDA as frontline therapies for chronic-phase CML. “When imatinib loses patent exclusivity in early 2016, 6 to 8 manufacturers are expected to enter the generic imatinib market,” said Dr Larson.
In evaluating the clinical outcomes and economic costs of imatinib versus second-generation TKIs as initial treatment for patients with newly diagnosed CML, Dr Larson’s group applied “value of information” as an outgrowth of comparative effectiveness methods to prospectively assess step therapy and physician’s choice. In step therapy, all patients begin with imatinib but are switched for intolerance or failure of efficacy. In the physician’s choice model, imatinib, dasatinib, and nilotinib were prescribed equally for initial therapy. “I believe this currently reflects the situation in the United States,” said Dr Larson.
The results were evaluated from a commercial payer perspective, with comparison of treatment costs and outcomes over the first 5 years of therapy. The end points used for this analysis were complete cytogenetic response (CCyR) at 12 months and overall survival.
In the step therapy model, if imatinib failed or was not tolerated as the initial choice, patients were switched to dasatinib or to nilotinib in equal proportions. In the physician’s choice model, if the initial second-generation TKI failed, patients were switched to an alternate second-generation TKI (with a small percentage switched to imatinib).
Patients with CCyR by 12 months continued to receive initial TKI therapy up to complete remission and were assumed to survive for 5 years. It was assumed that patients without CCyR by 12 months were switched to an alternate TKI and also survived for 5 years. Patients who progressed to accelerated-phase CML or blast crisis CML (an estimated 5% of patients) received allogeneic transplantation, assuming a 1-year survival of 50%.
The model assumed an annual cost of $60,390 for imatinib, $95,338 for dasatinib, and $91,644 for nilotinib. The cost of imatinib was assumed to decrease with its availability as a generic, remaining at 100% of the branded drug price for the first 6 months, 60% to 80% of the branded-drug price in the second 6 months, and 10% to 30% thereafter.
The 12-month CCyR model showed that step therapy costs less and offers clinically equivalent utility compared with physician’s choice over the first 5 years (with step therapy at approximately $184,000 vs physician’s choice at $216,000). The QALYs remained similar between step therapy and physician’s choice (3.25 vs 3.36, respectively).
Step therapy was estimated to have an incremental cost-effectiveness ratio of $291,000 per QALY. Multivariate probabilistic sensitivity analyses found step therapy to be cost-effective in 73.3% of 10,000 Monte Carlo simulations, with the currently accepted willingness-to-pay threshold of $100,000 per QALY.