Assessment of Dasatinib Versus Nilotinib as Upfront Therapy for Chronic Phase of Chronic Myeloid Leukemia in Qatar: A Cost-Effectiveness Analysis

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Abstract

Background:

The economic outcome research of approved tyrosine kinase inhibitors for treating the chronic phase of chronic myeloid leukemia in developing is scarce. The aim of this study was to assess the cost-effectiveness of dasatinib and nilotinib for newly diagnosed chronic myeloid leukemia patients.

Methods:

A decision tree model was developed linking clinical effectiveness (defined as major molecular response) and/or complete cytogenetic response, utility, and cost data over a 12-month period. Patients are recruited from Qatar Cancer Registry. The probability of primary clinical outcome is calculated from DASISION (dasatinib) and ENESTnd (nilotinib) trials. Direct healthcare costs were derived from the national healthcare payer system, whereas adverse effects data were derived from local incident reporting system.

Results:

In the first-line treatments of chronic myeloid leukemia patients, nilotinib has greater major molecular response (39% nilotinib vs 12% dasatinib) and complete cytogenetic response (24% nilotinib vs 16% dastinib) response outcomes, and more adverse effects than dasatinib (13.3% vs 4%). Moreover, nilotinib is more cost-effective with annual costs (USD63,589.59) and after 12 months of follow-up. Despite the lower acquisition annual cost of dasatinib (USD59,486.30), the incremental cost-effectiveness ratio of nilotinib (vs dasatinib) per major molecular response/complete cytogenetic response achieved was USD15,481.10 per year. There were no cases in both arms that progressed to accelerated or blast phase. At a threshold of 3 times gross domestic product per capita of Qatar and according to World Health Organization recommendation, the nilotinib use is still cost-effective.

Conclusion:

Upfront therapy of chronic myeloid leukemia–chronic phase patients by nilotinib plan appears to be more cost-effective than dasatinib.

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Most cited references 24

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European LeukemiaNet 2020 recommendations for treating chronic myeloid leukemia

A Hochhaus, M Baccarani, R Silver … (2020)

The therapeutic landscape of chronic myeloid leukemia (CML) has profoundly changed over the past 7 years. Most patients with chronic phase (CP) now have a normal life expectancy. Another goal is achieving a stable deep molecular response (DMR) and discontinuing medication for treatment-free remission (TFR). The European LeukemiaNet convened an expert panel to critically evaluate and update the evidence to achieve these goals since its previous recommendations. First-line treatment is a tyrosine kinase inhibitor (TKI; imatinib brand or generic, dasatinib, nilotinib, and bosutinib are available first-line). Generic imatinib is the cost-effective initial treatment in CP. Various contraindications and side-effects of all TKIs should be considered. Patient risk status at diagnosis should be assessed with the new EUTOS long-term survival (ELTS)-score. Monitoring of response should be done by quantitative polymerase chain reaction whenever possible. A change of treatment is recommended when intolerance cannot be ameliorated or when molecular milestones are not reached. Greater than 10% BCR-ABL1 at 3 months indicates treatment failure when confirmed. Allogeneic transplantation continues to be a therapeutic option particularly for advanced phase CML. TKI treatment should be withheld during pregnancy. Treatment discontinuation may be considered in patients with durable DMR with the goal of achieving TFR.

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Nilotinib versus imatinib for the treatment of patients with newly diagnosed chronic phase, Philadelphia chromosome-positive, chronic myeloid leukaemia: 24-month minimum follow-up of the phase 3 randomised ENESTnd trial.

Giuseppe Saglio, I Flinn, Gianantonio Rosti … (2011)

Nilotinib has shown greater efficacy than imatinib in patients with newly diagnosed Philadelphia chromosome-positive chronic myeloid leukaemia (CML) in chronic phase after a minimum follow-up of 12 months. We present data from the Evaluating Nilotinib Efficacy and Safety in clinical Trials-newly diagnosed patients (ENESTnd) study after a minimum follow-up of 24 months. ENESTnd was a phase 3, multicentre, open-label, randomised study. Adult patients were eligible if they had been diagnosed with chronic phase, Philadelphia chromosome-positive CML within the previous 6 months. Patients were randomly assigned (1:1:1) to receive nilotinib 300 mg twice a day, nilotinib 400 mg twice a day, or imatinib 400 mg once a day, all administered orally, by use of a computer-generated randomisation schedule, using permuted blocks, and stratified according to Sokal score. Efficacy results are reported for the intention-to-treat population. The primary endpoint was major molecular response at 12 months, defined as BCR-ABL transcript levels on the International Scale (BCR-ABL(IS)) of 0·1% or less by real-time quantitative PCR in peripheral blood. This study is registered with ClinicalTrials.gov, number NCT00471497. 282 patients were randomly assigned to receive nilotinib 300 mg twice daily, 281 to receive nilotinib 400 mg twice daily, and 283 to receive imatinib. By 24 months, significantly more patients had a major molecular response with nilotinib than with imatinib (201 [71%] with nilotinib 300 mg twice daily, 187 [67%] with nilotinib 400 mg twice daily, and 124 [44%] with imatinib; p<0·0001 for both comparisons). Significantly more patients in the nilotinib groups achieved a complete molecular response (defined as a reduction of BCR-ABL(IS) levels to ≤0·0032%) at any time than did those in the imatinib group (74 [26%] with nilotinib 300 mg twice daily, 59 [21%] with nilotinib 400 mg twice daily, and 29 [10%] with imatinib; p<0·0001 for nilotinib 300 mg twice daily vs imatinib, p=0·0004 for nilotinib 400 mg twice daily vs imatinib). There were fewer progressions to accelerated or blast phase on treatment, including clonal evolution, in the nilotinib groups than in the imatinib group (two with nilotinib 300 mg twice daily, five with nilotinib 400 mg twice daily, and 17 with imatinib; p=0·0003 for nilotinib 300 mg twice daily vs imatinib, p=0·0089 for nilotinib 400 mg twice daily vs imatinib). At 24 months, survival was comparable in all treatment groups, but fewer CML-related deaths had occurred in both the nilotinib groups than in the imatinib group (five with nilotinib 300 mg twice daily, three with nilotinib 400 mg twice daily, and ten with imatinib). Overall, the only grade 3 or 4 non-haematological adverse events that occurred in at least 2·5% of patients were headache (eight [3%] with nilotinib 300 mg twice daily, four [1%] with nilotinib 400 mg twice daily, and two [<1%] with imatinib) and rash (two [<1%], seven [3%], and five [2%], respectively). Grade 3 or 4 neutropenia was more common with imatinib than with either dose of nilotinib (33 [12%] with nilotinib 300 mg twice daily, 30 [11%] with nilotinib 400 mg twice daily, and 59 [21%] with imatinib). Serious adverse events were reported in eight additional patients in the second year of the study (four with nilotinib 300 mg twice daily, three with nilotinib 400 mg twice daily, and one with imatinib). Nilotinib continues to show better efficacy than imatinib for the treatment of patients with newly diagnosed CML in chronic phase. These results support nilotinib as a first-line treatment option for patients with newly diagnosed disease. Novartis. Copyright © 2011 Elsevier Ltd. All rights reserved.

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Past, present, and future of Bcr-Abl inhibitors: from chemical development to clinical efficacy

Federico Rossari, Filippo Minutolo, Enrico Orciuolo (2018)

Bcr-Abl inhibitors paved the way of targeted therapy epoch. Imatinib was the first tyrosine kinase inhibitor to be discovered with high specificity for Bcr-Abl protein resulting from t(9, 22)-derived Philadelphia chromosome. Although the specific targeting of that oncoprotein, several Bcr-Abl-dependent and Bcr-Abl-independent mechanisms of resistance to imatinib arose after becoming first-line therapy in chronic myelogenous leukemia (CML) treatment. Consequently, new specific drugs, namely dasatinib, nilotinib, bosutinib, and ponatinib, were rationally designed and approved for clinic to override resistances. Imatinib fine mechanisms of action had been elucidated to rationally develop those second- and third-generation inhibitors. Crystallographic and structure-activity relationship analysis, jointly to clinical data, were pivotal to shed light on this topic. More recently, preclinical evidence on bafetinib, rebastinib, tozasertib, danusertib, HG-7-85-01, GNF-2, and 1,3,4-thiadiazole derivatives lay promising foundations for better inhibitors to be approved for clinic in the near future. Notably, structural mechanisms of action and drug design exemplified by Bcr-Abl inhibitors have broad relevance to both break through resistances in CML treatment and develop inhibitors against other kinases as targeted chemotherapeutics.

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Author and article information

Journal

Journal ID (nlm-ta): Cancer Control

Journal ID (publisher-id): CCX

Journal ID (hwp): spccx

Title: Cancer Control : Journal of the Moffitt Cancer Center

Publisher: SAGE Publications (Sage CA: Los Angeles, CA )

ISSN (Print): 1073-2748

ISSN (Electronic): 1526-2359

Publication date (Electronic): 23 April 2021

Publication date Collection: Jan-Dec 2021

Volume: 28

Electronic Location Identifier: 10732748211001796

Affiliations

[1 ]Pharmacy Department, National Center for Cancer Care and Research, HMC, Doha, Qatar

[2 ]Pharmacy Department, Women Wellness and Research Center, HMC, Doha, Qatar

[3 ]Hematology Department, National Center for Cancer Care and Research, HMC, Doha, Qatar

[4 ]College of Pharmacy, QU Health, Ringgold 61780, universityQatar University; , Doha, Qatar

[5 ]College of Medicine, Ringgold 61780, universityQatar University; , Doha, Qatar

Author notes

[*]Mohamed Yassin, Hematology Department, National Center for Cancer Care and Research, HMC, Doha, Qatar; College of Medicine, Qatar University, Doha, Qatar. Email: yassinmoha@ 123456gmail.com .

Author information

Mohamed Yassin https://orcid.org/0000-0002-1144-8076

Article

Publisher ID: 10.1177_10732748211001796

DOI: 10.1177/10732748211001796

PMC ID: 8204580

PubMed ID: 33887995

SO-VID: 92665741-61fe-47a6-ba00-ab20f6f12ca3

License:

This article is distributed under the terms of the Creative Commons Attribution-NonCommercial 4.0 License ( https://creativecommons.org/licenses/by-nc/4.0/) which permits non-commercial use, reproduction and distribution of the work without further permission provided the original work is attributed as specified on the SAGE and Open Access pages ( https://us.sagepub.com/en-us/nam/open-access-at-sage).

History

Date received : 13 January 2021

Date revision received : 13 January 2021

Date accepted : 16 February 2021

Funding

Funded by: Qatar Foundation, https://doi.org/10.13039/100007458;

Award ID: Qatar national library

Custom metadata

cover-date January-December 2021

typesetter ts3

Keywords: cancer,chronic myeloid leukemia,tyrosine kinase inhibitors,nilotinib,dasatinib,leukemia

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Keywords: cancer, chronic myeloid leukemia, tyrosine kinase inhibitors, nilotinib, dasatinib, leukemia

Assessment of Dasatinib Versus Nilotinib as Upfront Therapy for Chronic Phase of Chronic Myeloid Leukemia in Qatar: A Cost-Effectiveness Analysis

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Abstract

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Results:

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Cancer Immunotherapy

Most cited references 24

European LeukemiaNet 2020 recommendations for treating chronic myeloid leukemia

Nilotinib versus imatinib for the treatment of patients with newly diagnosed chronic phase, Philadelphia chromosome-positive, chronic myeloid leukaemia: 24-month minimum follow-up of the phase 3 randomised ENESTnd trial.

Past, present, and future of Bcr-Abl inhibitors: from chemical development to clinical efficacy

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