Cost-effectiveness of Tyrosine Kinase Inhibitor Treatment Strategies for Chronic Myeloid Leukemia in Chronic Phase After Generic Entry of Imatinib in the United States

Padula, William V.; Larson, Richard A.; Dusetzina, Stacie B.; Apperley, Jane F.; Hehlmann, Rüdiger; Baccarani, Michele; Eigendorff, Ekkehard; Guilhot, Joëlle; Mahon, François Xavier; Martinelli, Giovanni; Mayer, Jiřı́; Müller, Martin C.; Niederwieser, Dietger; Saußele, Susanne; Schiffer, Charles A.; Silver, Richard T.; Simonsson, Bengt; Conti, Rena M.

doi:10.1093/jnci/djw003

Cited by 84 publications

(71 citation statements)

References 49 publications

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“…The analysis showed an incremental costeffectiveness ratio for the imatinib-first strategy of US$883 730. 26 One important element that should be added to these analyses is the potential for treatment discontinuation. As mentioned above, eligibility for this strategy is augmented by approximately 15% by the initial use of nilotinib compared with imatinib.…”

Section: Cost-effectivenessmentioning

confidence: 99%

Chronic myeloid leukemia: sequencing of TKI therapies

Cortes

Kantarjian

2016

Hematology

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Multiple tyrosine kinase inhibitors (TKIs) are available for managing patients with chronic myeloid leukemia. Although most patients have a favorable outcome with their initial therapy, whether imatinib or a second-generation TKI was used, some will require subsequent use of one or more different TKIs. Such sequencing might be indicated in a reactive way (ie, for patients who have experienced resistance or intolerance to their initial therapy) or in a proactive way (ie, for patients with a somewhat favorable outcome who have not reached an "optimal" outcome). Sequencing of TKIs has become standard practice, and the proper use of sequenced TKIs is likely to optimize outcomes and resource utilization. Learning Objectives• Assess the different scenarios in which TKI sequencing can be used in patients with chronic myeloid leukemia • Critically review the outcomes associated with sequencing of TKI in patients with chronic myeloid leukemia Tyrosine kinase inhibitors (TKIs) became standard therapy for patients with chronic myeloid leukemia (CML) not long after the first patient received STI571 (later known as imatinib mesylate) on a phase I clinical trial. 1 The initial approved indication was for patients with resistance to or intolerance of interferon alpha-based therapy, the standard at the time. By 2003, imatinib was approved as frontline therapy for CML, 2 and since then, nearly all patients with access to TKIs have received them as initial therapy. Shortly thereafter, secondgeneration agents, including dasatinib, nilotinib, and bosutinib, with increased potency, different structures that allowed them to overcome most mutations leading to resistance to TKIs, and different toxicity profiles, were introduced and eventually received regulatory approval. Later, ponatinib, a drug with activity against T315I and all mutations tested, proved effective in overcoming resistance in most patients, even those who had received 3 or more prior TKIs. All TKIs were eventually compared with imatinib in the first-line setting, and they generally demonstrated higher response rates, with deeper and faster responses which, in the case of dasatinib and nilotinib, were sufficient to lead to their approval as initial therapy for patients with chronic phase CML (CML-CP). This rapid development has resulted in the availability of multiple TKIs, and along with this, the sequential use of various TKIs in patients with CML-CP (Figure 1).The use of sequential TKI therapy, regardless of the choice of initial therapy, is perhaps more common than is usually appreciated. Despite the professed efficacy of initial therapy with TKIs, at least onethird of all patients initially treated in clinical trials with any TKI for newly diagnosed CML, whether imatinib or a second-generation TKI, have received at least one additional TKI. After 5 years of follow-up in the DASISION trial (in the final report), 39% of patients initially treated with dasatinib and 37% of those treated with imatinib are no longer receiving their initial therapy.3 Similarly, the 5-ye...

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Section: Cost-effectivenessmentioning

confidence: 99%

Chronic myeloid leukemia: sequencing of TKI therapies

Cortes

Kantarjian

2016

Hematology

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“…Sacha et al demonstrated non-inferiority of generic imatinib in clinical efficacy and tolerability compared to branded imatinib in Poland at a significantly lower cost [30]. Padula et al [6] used Markov models to compare the 5-year cost-effectiveness of an 'imatinib first' (i.e. step-edit) versus 'physician's choice' that allowed for the initiation of any one of the three TKIs approved for first-line use, in achieving complete cytogenetic response (CCyR) and early molecular response (EMR).…”

Section: Generic Imatinib Step Editmentioning

confidence: 99%

“…First, the model allowed only one opportunity to switch within the first 12 months after treatment initiation during a 5-year time horizon [6]. NCCN guidelines recommend regular evaluations of the response to treatment every 3-6 months depending on time on therapy.…”

Section: Generic Imatinib Step Editmentioning

confidence: 99%

“…The Gleevec ® loss of exclusivity (LOE) in the USA brought about the entry of the first generic imatinib in February 2016 and with it, extensive attention from both payers and researchers due to potential cost savings that could be achieved through generic substitution of the branded agent [6][7][8] or by instituting utilization management policies like step edits and/or prior authorizations [6,7]. Generic substitution of a branded agent is most commonly a prescriber-and pharmacist-driven process that is governed by a combination of federal and state mandates.…”

Section: Introductionmentioning

confidence: 99%

See 1 more Smart Citation

The value of open access and a patient centric approach to oral oncolytic utilization in the treatment of Chronic Myelogenous Leukemia: A U.S. perspective

Das¹,

Gitlin²,

Siegartel

et al. 2017

Expert Review of Pharmacoeconomics & Outcomes Research

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“…Anticipating the introduction of generic imatinib into the USA, Padula and colleagues 3 conducted an analysis to estimate the cost-effectiveness of chronic phase CML therapy over a 5-year timeframe (2016–2021). The investigators compared upfront generic imatinib with ‘physician choice’ of frontline treatment using one of three TKIs, selected randomly: dasatinib (Sprycel), nilotinib (Tasigna), or patented imatinib (Gleevec) 3 .…”

mentioning

confidence: 99%