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

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.

Population-based utilization and costs associated with tyrosine kinase inhibitors for first-line treatment of chronic myelogenous leukemia among elderly patients.

BACKGROUND: Following approval of imatinib, a breakthrough tyrosine kinase inhibitor (TKI), survival significantly improved by more than 20% since 2001 among treated chronic myelogenous leukemia (CML) patients. Subsequently, more expensive second-generation TKIs with varying selectivity profiles have been approved. Population-based studies are needed to evaluate the real-world utilization of TKI therapies, particularly given their escalating costs and recommendations for maintenance therapy. OBJECTIVE: To assess the utilization patterns of first-line TKIs, overall and by specific agent, among elderly CML patients in the United States, and the cost implications. METHODS: CML patients aged 65 years and older at diagnosis between 2007 and 2015 were identified from population-based cancer registries in the linked Surveillance, Epidemiology, and End Results (SEER)-Medicare database. The percentage of CML patients receiving imatinib, dasatinib, or nilotinib within the first year of diagnosis was calculated along with time to first-line treatment initiation. Bivariate comparisons and Cox proportional hazards models were used to identify factors associated with TKI initiation. Average monthly patient responsibility, including patient out-of-pocket (OOP) costs, stratified by Part D low-income subsidy (LIS) status were also calculated. RESULTS: Among the 1,589 CML patients included, receipt of any TKI within 1 year of diagnosis increased from 66.2% to 78.9%. In 2015, the distribution of first-line TKI therapies was 41.3% imatinib, 28.3% dasatinib, and 9.3% nilotinib. Almost 60% of patients initiated TKI treatment within 3 months of diagnosis. Multivariable analysis indicated that TKI use in the first year was lower among the very elderly (aged > 75 years vs. 65-69 years: HR = 0.72; 95% CI = 0.63-0.83), patients with more comorbidities (Hierarchical Condition Category risk score > 2 vs. HR = 0.74, 95% CI = 0.62-0.88), and patients ineligible for LIS (HR = 0.75; 95% CI = 0.65-0.87). Average monthly patient OOP cost was significantly lower for LIS-eligible versus LIS-ineligible patients: imatinib (2016: $12 vs. $487), dasatinib (2016: $34 vs. $557), and nilotinib (2016: $1 vs. $526). CONCLUSIONS: TKI use has increased significantly since 2007. While imatinib remained the most frequently prescribed first-line agent, by 2015 newer TKIs represented one third of the market share. Utilization patterns indicated persistent age, comorbidity, and financial barriers. TKI use is indicated for long-term therapy, and increased adoption of newer, more expensive agents raises concerns about the sustained affordability of CML treatment, particularly among unsubsidized patients. DISCLOSURES: No outside funding supported this study. There are no reported conflicts of interest.

Cost-Effectiveness of First-Line Tyrosine Kinase Inhibitor Therapy Initiation Strategies for Chronic Myeloid Leukemia.

OBJECTIVES: Overall survival in chronic myeloid leukemia (CML) in chronic phase is not significantly different by treatment with first-line tyrosine kinase inhibitors (TKIs), but emerging evidence reveals differences in costs and safety profiles. We evaluated the 1-year cost-effectiveness of TKI initiation with imatinib, dasatinib, or nilotinib among a hypothetical cohort of incident patients with CML from a US payer's perspective. METHODS: We constructed a decision analytic model to assess quality-adjusted life years (QALYs), healthcare costs, net monetary benefit, and incremental cost-effectiveness of treatment strategies. We used published studies and data from the IBM Watson Health MarketScan database for model parameters. To calculate TKI costs, we used the 2018 Federal Supply Schedule estimates for generic imatinib and branded second-generation TKIs. We evaluated cost-effectiveness under various willingness-to-pay thresholds. We accounted for uncertainty with deterministic and probabilistic sensitivity analyses. RESULTS: In the base-case analysis, imatinib was favored over dasatinib and nilotinib at a lower cost per QALY gained. Imatinib remained the favored strategy after 1-way variations in TKI costs, TKI switching, QALYs, adverse event risk, and CML progression. When we assessed model uncertainty with prespecified parameter distributions, imatinib was cost-saving compared with dasatinib in 40% of 100 0000 simulations and was favored over all simulations compared with nilotinib. First-line treatment with second-generation TKIs was cost-effective in 50% of simulations at a $200 000/QALY willingness-to-pay threshold. CONCLUSIONS: Generic availability of imatinib provides a more cost-effective treatment approach in the first year compared with other available TKIs for newly diagnosed patients with CML.

Tyrosine Kinase Inhibitors and the Relationship With Adherence, Costs, and Health Care Utilization in Commercially Insured Patients With Newly Diagnosed Chronic Myeloid Leukemia: A Retrospective Claims-Based Study.

OBJECTIVE: To examine the association among tyrosine kinase inhibitor (TKI) out-of-pocket costs, adherence, and health care costs and utilization in a large group of commercially insured patients with chronic myeloid leukemia (CML). MATERIALS AND METHODS: Patients with CML aged 18 to 64 years were identified using IBM MarketScan Commercial Database between April 1, 2011 and December 31, 2014. Patients were required to be continuously enrolled 3 months before and 12 months after TKI (imatinib, dasatinib, or nilotinib) initiation. TKI adherence is estimated using the proportion of days covered (PDC), defined as the percentage of the PDC by the prescription fill during the 12-month study period (adherent patients have PDC ≥80%). Health care cost differences between adherent and nonadherent patients were estimated using generalized linear models. Health care utilization was compared using negative binomial regression models. All models were controlled for potential confounding factors. RESULTS: The study sample consisted of 863 patients, where 355 (41.1%) patients were classified as adherent. Over the study period, nonadherent patients incurred US$10,974 more in medical costs (P<0.001), and US$1663 more in non-TKI pharmacy costs (P<0.01). Adherent patients incurred US$28,184 more in TKI pharmacy costs (P<0.001) that resulted in US$18,305 more in overall total health care costs (P<0.001). Adherent patients, however, were estimated to be less likely to have all-cause hospitalizations (incidence rate ratio, 0.32; P<0.001), or CML-specific hospitalizations (incidence rate ratio, 0.31; P<0.01). CONCLUSIONS: Patients with CML with better adherence experienced fewer hospitalizations, resulting in medical service cost savings. These lower medical costs, however, were more than offset by higher TKI medication costs observed during the first year of TKI therapy.

Budget Impact of Treatment-Free Remission in Treating Chronic-Phase Philadelphia-Positive Chronic Myeloid Leukemia in Lebanon.

PURPOSE: Chronic myeloid leukemia (CML) ranks second in terms of disease-related health care expenditures at the Lebanese Ministry of Public Health (MoPH) after breast cancer. With the introduction of tyrosine kinase inhibitors (TKIs), survival of patients with CML has dramatically improved and approached that of the normal population. In recent years, several studies demonstrated that patients who achieve a deep molecular response while receiving TKI therapy could safely attempt treatment-free remission (TFR), the new treatment goal in patients with CML. The objective is to estimate the budget impact of TFR at the MoPH. METHODS: Analyses were done on 162 patients with CML receiving imatinib, nilotinib, or dasatinib, as first-line or second-line therapy, over a 4-year time horizon using MoPH drug pricing. The model assumed that patients could attempt TFR after 36 months of TKI therapy, where the last 24 months were at stable molecular response as per MoPH and National Comprehensive Cancer Network guidelines. Duration of TFR was based on European Stop Kinase Inhibitor treatment-free survival curve. RESULTS: Out of the 162 patients, 83 were eligible to attempt TFR, 36 patients were not eligible, 32 patients were lost to follow-up, two patients died as a result of CML progression, and five died as a result of other causes. The total cost of CML treatment with TFR from the time of analysis and over 4 years can be reduced by more than 7 million US dollars (57%). CONCLUSION: The model can be used to inform health care decision makers on the importance of TFR and the potential savings.

Economic Evaluations of Tyrosine Kinase Inhibitors for Patients with Chronic Myeloid Leukemia in Middle- and High-Income Countries: A Systematic Review.

OBJECTIVES: The objective of this systematic review was to conduct a comprehensive assessment of economic evaluations of tyrosine kinase inhibitors (TKIs) in patients with chronic myeloid leukemia (CML) in middle- and high-income countries. METHODS: A literature search was conducted in Embase, MEDLINE (via PubMed) and the Cochrane library on March 3, 2018 to identify economic evaluations of chronic myeloid leukemia that met the inclusion criteria. Data on such parameters as patient characteristics, cost components, and main outcomes were extracted from eligible studies. RESULTS: The literature review retrieved 798 studies, 17 of which fulfilled the eligibility criteria. Eight studies included an economic analysis on newly diagnosed patients with CML. Seven studies investigated people with CML who were resistant or intolerant to standard-dose imatinib. One article focused on chronic phase (CP)-CML patients who experienced failure with first-line treatment for interferon-α. The last study investigated advanced stages of CML patients. Most studies (n = 70.6%) were conducted in high-income countries. Only five studies (n = 29.4%) were performed in middle-income countries. Most studies used a Markov model. The time horizon varied from six months to life-time. CONCLUSIONS: Despite high costs, the included studies indicate that imatinib regimens are cost effective in newly diagnosed patients with CP-CML. For people with CML who are resistant or intolerant to standard-dose imatinib, dasatinib is likely to be a more cost-effective strategy in middle-income countries. More studies are necessary to assess the long-term efficacy and cost effectiveness of novel treatment options.

Burden of Infections Among Chronic Myeloid Leukemia Patients Receiving Dasatinib or Nilotinib: A Real-World Retrospective Healthcare Claims Study in the United States.

INTRODUCTION: Tyrosine kinase inhibitors (TKI) have been demonstrated to prolong survival in patients with chronic myeloid leukemia (CML). However, TKIs may be associated with an increased risk of infections. This study compared healthcare resource utilization (HRU) and costs among patients with CML receiving dasatinib or nilotinib, with a focus on infection-related economic outcomes. METHODS: Two large administrative databases were used to identify adult patients newly diagnosed with CML who initiated dasatinib or nilotinib as first- (1L) or second-line (2L) therapy and were classified into the following 1L (dasatinib 1L/nilotinib 1L cohorts) or 2L (dasatinib 2L/nilotinib 2L) cohorts based on the initiated 1L/2L TKI therapy. Infection-related HRU and healthcare costs were compared between cohorts, separately for 1L and 2L. RESULTS: Cohorts included 1156 patients in the dasatinib 1L and 677 patients in the nilotinib 1L cohorts, 322 patients in the dasatinib 2L, and 207 in the nilotinib 2L cohorts. In 1L and 2L, infection-related HRU was higher for dasatinib than nilotinib cohorts. Infection-related inpatient (IP) days constituted a larger proportion of all-cause IP days in the 1L/2L dasatinib than 1L/2L nilotinib cohorts (dasatinib 1L/2L: 53%/58%; nilotinib 1L/2L: 50%/46%). Compared to the nilotinib cohort, the dasatinib cohort had higher all-cause total costs per patient per year by US$17,901 in 1L and $28,625 in 2L. Of the total cost difference, infection-related were $6048 (34%) in 1L and $28,192 (99%) in 2L, largely driven by IP cost differences (1L/2L: 96%/98%). CONCLUSIONS: Dasatinib was associated with higher HRU and healthcare costs compared to nilotinib, particularly related to infections. FUNDING: Novartis Pharmaceutical Corporation.

Out-of-Pocket Spending Not Associated with Oral Oncolytic Survival Benefit.

BACKGROUND: With total and out-of-pocket spending for oral oncolytics rising, there is increased interest in choosing oncology treatments based on their clinical value relative to cost. OBJECTIVE: To determine if out-of-pocket spending varied for higher versus lower benefit oral oncology drugs reimbursed by commercial insurers. METHODS: This study was a retrospective analysis of commercial insurer prescription drug claims filed between 2007 and 2014 for 13 oral oncolytics approved before 2009. We calculated mean monthly out-of-pocket payment for each fill by patient. We then categorized oral oncolytics by their overall and progression-free survival benefits for each FDA-approved indication, using evidence from published studies. We assessed the relationship of survival benefit with mean monthly out-of-pocket payment, adjusting for demographic and plan characteristics. RESULTS: Our population included 44,113 patients aged 18-65 years (mean 52.5 [SD 9.4]) with a cancer diagnosis who filled 731,354 prescriptions. The most commonly represented oncolytics were imatinib (37.4% of fills), lenalidomide (17.7% of fills), and dasatinib (10.0% of fills). Approximately 32.3% of fills were for drug-indication pairs with an overall survival benefit of 4+ years. In adjusted analyses, there was no clear pattern to suggest that out-of-pocket payments differed with drug indication-specific survival benefits. Drugs for indications providing > 0 to 1 year of overall survival benefit were significantly more likely to have a lower out-of-pocket payment versus those prescribed off-label, but there were no significant differences in out-of-pocket payments between drugs and associated indications in any other survival category versus drugs used off-label. CONCLUSIONS: Out-of-pocket payments for oral oncolytics were not clearly related to indication-specific value in commercially insured patients. This finding suggests that despite increased attention to value- and indication-based drug pricing, cost sharing for oral oncolytics does not currently reflect these goals. DISCLOSURES: This project was supported by Research Scholar Grant RSGI-14-030-01-CPHPS from the American Cancer Society; the NIH Building Interdisciplinary Research Careers in Women's Health (BIRCWH) K12 Program; the North Carolina Translational and Clinical Sciences Institute (UL1TR001111) Grant; and K24CA181510 from the National Cancer Institute. The authors have no disclosures. Data from this study were presented at the 2017 American Society for Clinical Oncology Annual Meeting on June 5, 2017, in Chicago, Illinois.

Generic Price Competition For Specialty Drugs: Too Little, Too Late?

The case of generic imatinib demonstrates several potential barriers to effective generic price competition for specialty prescription drugs, including fewer market entrants, smaller-than-expected price reductions, shifts in prescribing toward more expensive brand-name treatments, and limited uptake of the generic product.

Impact of Genetic Mutations and Health Plan Access to Therapies on Treatment Response and Drug Costs Related to Tyrosine Kinase Inhibitor Treatment Among Patients With Chronic Myelogenous Leukemia.

OBJECTIVES: This study assessed treatment responses and economic consequences of limiting access to the second-generation BCR-ABL1 tyrosine kinase inhibitors (2G-TKI), dasatinib and nilotinib, for treatment of chronic myelogenous leukemia, while taking into account frequencies of genetic mutations that exhibit different sensitivities to the 2G-TKIs. METHODS: Frequencies of BCR-ABL1 mutations and the impact of mutations on responses to 2G-TKIs were obtained from published literature and used as inputs in a decision analytics model. Complete hematologic response (CHR) and major cytogenetic response (MCyR) were estimated after 12 months of 2G-TKI treatment. Total annual 2G-TKI drug costs per CHR and MCyR were estimated and compared among 3 2G-TKI access scenarios: (1) open access to both 2G-TKIs; (2) access restricted to dasatinib (DASA-only); and (3) access restricted to nilotinib (NILO-only). RESULTS: Among a hypothetical cohort of 1000 2G-TKI-treated chronic myelogenous leukemia patients, the percentage of patients with CHR and MCyR were greatest for the open access plan (CHR: 93%, MCyR: 56%), followed by DASA-only (88%, 53%) and NILO-only (67%, 47%). Compared with the 2G-TKI costs per CHR in open access ($120,706/CHR), the costs were 5% higher ($126,753/CHR) in DASA-only and 41% higher ($169,990/CHR) in NILO-only. Likewise, compared with the 2G-TKI costs per MCyR in open access ($198,284/MCyR), the costs were 6% higher ($209,259/MCyR) in DASA-only and 22% higher ($241,515/MCyR) in NILO-only. CONCLUSION: Open access to both 2G-TKIs is associated with improved clinical and economic outcomes: greater treatment response rates (CHR and MCyR) and lower drug costs compared with restricted access to 2G-TKIs.

Cost Effectiveness of Imatinib, Dasatinib, and Nilotinib as First-Line Treatment for Chronic-Phase Chronic Myeloid Leukemia in China.

BACKGROUND AND OBJECTIVE: Tyrosine kinase inhibitors (TKIs) have obvious effects on chronic myeloid leukemia (CML), but they are expensive in China. Moreover, the overall cost of treatment of CML is high and the medical economic burden of patients with CML on the government is heavy. This study tested the cost effectiveness of imatinib, nilotinib, and dasatinib as first-line treatment in Chinese patients who were first diagnosed with chronic myeloid leukemia in the chronic phase (CML-CP). METHODS: A state-transition Markov model combining clinical effectiveness, utility, and cost data was used. Sensitivity analyses were conducted to determine the robustness of the model outcomes. RESULTS: The imatinib-first, dasatinib-first, and nilotinib-first strategy offered patients 9.76, 9.87, and 9.72 quality-adjusted life years (QALYs) at a cost of US$303,502.42, US$381,681.03, and US$305,509.92 over 20 years, respectively. The nilotinib-first strategy exhibited the lowest utility and highest price and was thus eliminated. An incremental cost-effectiveness analysis of the imatinib-first strategy and the dasatinib-first strategy showed that the dasatinib-first strategy yielded an incremental cost-utility ratio (ICER) of 710,714.64 $/QALY compared with the imatinib-first strategy, which exceeded the threshold; hence, the dasatinib-first strategy was not cost effective and was eliminated. The results were robust for multiple sensitivity analyses. CONCLUSION: From the perspective of the Chinese medical system, imatinib is likely to be more cost effective than dasatinib and nilotinib for patients who were first diagnosed with CML-CP.

An economic analysis of high-dose imatinib, dasatinib, and nilotinib for imatinib-resistant chronic phase chronic myeloid leukemia in China: A CHEERS-compliant article.

BACKGROUND: The aim of the study was to test the cost-effectiveness of dasatinib compared to high-dose imatinib and nilotinib in Chinese patients who were diagnosed with imatinib-resistant chronic myeloid leukemia in the chronic phase (CML-CP). METHODS: A Markov model combined with clinical effectiveness, utility, and cost data was used. The sensitivity analyses were conducted to determine the robustness of the model outcomes. The impact of patient assistance programs (PAPs) was assessed. RESULTS: Treatment with dasatinib is expected to produce 3.65, 0.59, and 0.15 more quality-adjusted life years (QALYs) in comparison with high-dose imatinib (600 and 800 mg) and nilotinib, respectively. When a PAP was available, dasatinib yielded an incremental cost of $16,417 per QALY compared to imatinib (600 mg) and was cost-saving compared to imatinib (800 mg) and nilotinib. CONCLUSION: When PAP is available in the Chinese setting, dasatinib is likely to be a cost-effective strategy for patients with CML-CP standard-dose imatinib resistance. The results should be carefully explained due to the assumptions and limitations used in the study.

Healthcare and economic burden of adverse events among patients with chronic myelogenous leukemia treated with BCR-ABL1 tyrosine kinase inhibitors.

OBJECTIVES: BCR-ABL1 tyrosine kinase inhibitors (TKIs) are established treatments for chronic myelogenous leukemia (CML); however, they are associated with infrequent, but clinically serious adverse events (AEs). The objective of this analysis was to assess healthcare resource utilization and costs associated with AEs, previously identified using the FDA Adverse Event Reporting System (FAERS) in another study, among TKI-treated patients. METHODS: Adult patients with ≥1 inpatient or ≥2 outpatient ICD-9-CM diagnosis codes for CML and ≥1 claim for a TKI treatment between January 1, 2006 and September 30, 2012 were identified from the Commercial and Medicare MarketScan databases. The first claim for a TKI was designated as the index event. Patients were required to have no TKI treatment during a 12-month baseline period. Healthcare resource utilization and costs associated with select AEs having the strongest association with TKI treatment (femoral arterial stenosis [FAS], peripheral arterial occlusive disease [PAOD], intermittent claudication, coronary artery stenosis [CAS], pericardial effusion, pleural effusion, malignant pleural effusion, conjunctival hemorrhage) were evaluated during a 12-month follow-up period. RESULTS: The study sample included 2,005 CML patients receiving TKI therapy (mean age = 56 years; 56% male). Among all evaluated AEs, the highest mean inpatient healthcare costs were observed for FAS ($16,800 per patient) and PAOD ($14,263 per patient), which had total mean medical costs (inpatient + outpatient) of $17,015 and $15,154 per patient, respectively. Mean outpatient healthcare costs were highest for CAS ($1,861 per patient), followed by intermittent claudication ($947 per patient), PAOD ($891 per patient), and pleural effusion ($890 per patient). Total mean medical costs for fluid retention-related AEs, including pericardial effusion and pleural effusion, were $2,797 and $1,908 per patient, respectively. CONCLUSIONS: The healthcare costs of AEs identified in the FAERS as having the strongest association with TKI treatment are substantial. Vascular stenosis-related AEs, including FAS and PAOD, have the highest cost burden.

Estimated generic prices of cancer medicines deemed cost-ineffective in England: a cost estimation analysis.

OBJECTIVES: The aim of this study was to estimate lowest possible treatment costs for four novel cancer drugs, hypothesising that generic manufacturing could significantly reduce treatment costs. SETTING: This research was carried out in a non-clinical research setting using secondary data. PARTICIPANTS: There were no human participants in the study. Four drugs were selected for the study: bortezomib, dasatinib, everolimus and gefitinib. These medications were selected according to their clinical importance, novel pharmaceutical actions and the availability of generic price data. PRIMARY AND SECONDARY OUTCOME MEASURES: Target costs for treatment were to be generated for each indication for each treatment. The primary outcome measure was the target cost according to a production cost calculation algorithm. The secondary outcome measure was the target cost as the lowest available generic price; this was necessary where export data were not available to generate an estimate from our cost calculation algorithm. Other outcomes included patent expiry dates and total eligible treatment populations. RESULTS: Target prices were £411 per cycle for bortezomib, £9 per month for dasatinib, £852 per month for everolimus and £10 per month for gefitinib. Compared with current list prices in England, these target prices would represent reductions of 74-99.6%. Patent expiry dates were bortezomib 2014-22, dasatinib 2020-26, everolimus 2019-25 and gefitinib 2017. The total global eligible treatment population in 1 year is 769 736. CONCLUSIONS: Our findings demonstrate that affordable drug treatment costs are possible for novel cancer drugs, suggesting that new therapeutic options can be made available to patients and doctors worldwide. Assessing treatment cost estimations alongside cost-effectiveness evaluations is an important area of future research.

Nilotinib versus dasatinib as second-line therapy in patients with Philadelphia chromosome-positive chronic myeloid leukemia in chronic phase who are resistant or intolerant to imatinib: a cost-effectiveness analysis based on real-world data.

OBJECTIVE: To evaluate the cost-effectiveness of second-line nilotinib vs dasatinib among patients with Philadelphia chromosome-positive chronic myeloid leukemia in chronic phase (Ph+ CML-CP) who are resistant or intolerant to imatinib, from a US third-party perspective. METHODS: A lifetime partitioned survival model was developed to compare the costs and effectiveness of nilotinib vs dasatinib, which included four health states: CP on treatment, CP post-discontinuation, progressive disease (accelerated phase [AP] or blast crisis [BC]), and death. Time on treatment, progression-free survival, and overall survival of nilotinib and dasatinib were estimated using real-world comparative effectiveness data. Parametric survival models were used to extrapolate outcomes beyond the study period. Drug treatment costs, medical costs, and adverse event costs were obtained from the literature and publicly available databases. Utilities of health states were derived from the literature. Incremental cost-effectiveness ratios, including incremental cost per life-year (LY) gained and incremental cost per quality-adjusted life-year (QALY) gained, were estimated comparing nilotinib and dasatinib. Deterministic sensitivity analyses were performed by varying patient characteristics, cost, and utility inputs. RESULTS: Over a lifetime horizon, nilotinib-treated patients were associated with 11.7 LYs, 9.1 QALYs, and a total cost of $1,409,466, while dasatinib-treated patients were associated with 9.5 LYs, 7.3 QALYs, and a total cost of $1,422,122. In comparison with dasatinib, nilotinib was associated with better health outcomes (by 2.2 LYs and 1.9 QALYs) and lower total costs (by $12,655). Deterministic sensitivity analysis results showed consistent findings in most scenarios. LIMITATIONS: In the absence of long-term real-world data, the lifetime projection could not be validated. CONCLUSIONS: Compared with dasatinib, second-line nilotinib was associated with better life expectancy, better quality-of-life, and lower costs among patients with Ph+ CML-CP who were resistant or intolerant to imatinib.

Treatment patterns and healthcare costs among newly-diagnosed patients with chronic myeloid leukemia receiving dasatinib or nilotinib as first-line therapy in the United States.

OBJECTIVE: To compare treatment patterns and economic outcomes of dasatinib and nilotinib as 1st-line therapies for chronic myeloid leukemia (CML). METHODS: Adult CML patients initiated on first-line dasatinib or nilotinib in 2010-2014 were identified from two large US administrative claims databases. Treatment patterns, tyrosine kinase inhibitor (TKI) adherence and healthcare resource utilization (HRU) and costs were measured from the 1st-line TKI initiation (index date) to the end of follow-up. RESULTS: A total of 604 and 418 patients were included in the dasatinib and nilotinib cohorts (mean ages = 50.9 and 52.5 years, 46.4% and 45.7% female), respectively. Among the dasatinib patients, 91% started with 100 mg/day, 3% with <100 mg/day, and 6% with >100 mg/day. Among the nilotinib patients, 76% started with 600 mg/day, 16% with >600 mg/day, and 8% <600 mg/day. The dasatinib cohort had a higher hazard of dose decrease (hazard ratio [HR] = 1.66; p = .002) and of switching to another TKI (HR =1.62; p = .019) compared to the nilotinib cohort. The hazard of dose increase (HR =0.76; p = .423) and treatment discontinuation (HR =1.10; p = .372) were not significantly different between cohorts. There was also no significant difference in TKI adherence levels (mean proportion of days covered [PDC] difference over first 6 months = -0.0003, p = .981; mean PDC difference over first 12 months = -0.0022, p = .880) and HRU (inpatient day incidence rate ratio [IRR] = 1.03, p = .930; emergency room IRR =1.26, p = .197; and days with outpatient services IRR = 1.01, p = .842). The dasatinib cohort incurred higher healthcare costs by $749 per patient per month (p = .044) compared to the nilotinib cohort. LIMITATION: Information on CML phase and Sokal score was not available. CONCLUSIONS: Dasatinib was associated with an increased hazard of dose decrease and switching to another TKI and higher healthcare costs, vs nilotinib.

Cost-effectiveness analysis of second-line tyrosine kinase inhibitor treatment for chronic myelogenous leukemia.

AIM: A cost-effectiveness analysis was performed for sequential treatments of chronic myelogenous leukemia (CML) with tyrosine kinase inhibitors (TKIs) after failure of 1st line imatinib, from a commercial payer perspective in the US. METHODS: A Markov model was developed to simulate lifetime treatment costs and health outcomes for TKI sequences for treatment of patients resistant or intolerant to 1st-line imatinib. Five health states were included, chronic phase 2nd-line TKI, chronic phase 3rd-line TKI, chronic phase post-TKI, advanced phases, and death. Efficacy (response achievement, loss of response, transformation, death) and safety (adverse events incidence, discontinuation) data are based on clinical trials. Resource utilization, costs, and utilities were based on product labels and publically available data. Uncertainty analyses were conducted for key inputs. RESULTS: In patients failing imatinib, dasatinib-initiating treatment sequences provide the most survival (ΔLYs = 0.2-2.0), QALYs (ΔQALYs = 0.2-1.9), and accrue highest CML-related costs (ΔCosts = $64,000-$222,000). The average ICER per QALY for dasatinib- vs imatinib-initiating sequences is $100,000 for an imatinib-resistant population. The average ICER per QALY for dasatinib- vs nilotinib-initiating sequences is $170,000 for an imatinib-resistant population, and $160,000 for an imatinib-intolerant population. CONCLUSIONS: This analysis suggests that dasatinib is associated with increased survival and quality of life compared to high dose imatinib and to a smaller extent with nilotinib, among patients resistant or intolerant to 1st-line imatinib, primarily based on higher cytogenetic response rates observed in clinical studies of dasatinib. Head-to-head studies of sequential use of dasatinib and nilotinib are needed to validate the model findings of improved survival (LYs) with better quality-of-life (QALYs) for patients initiating dasatinib in 2nd-line. However, the model findings (in light of higher cytogenetic response rates with dasatinib) are supported by other studies showing improved quality-of-life for responders, and improved survival for patients achieving cytogenetic response.

Cost-utility analysis of dasatinib and nilotinib in patients with chronic myeloid leukemia refractory to first-line treatment with imatinib in Thailand.

BACKGROUND: Recently, the second-generation tyrosine kinase inhibitors dasatinib and nilotinib have emerged as alternative treatments in patients with chronic myeloid leukemia (CML) who are resistant to or intolerant of imatinib. OBJECTIVE: This article aimed to assess the cost utility and budget impact of using dasatinib or nilotinib, rather than high-dose (800-mg/d) imatinib, in patients with chronic phase (CP) CML who are resistant to standard-dose (400-mg/d) imatinib in Thailand. METHODS: A Markov simulation model was developed and used to estimate the lifetime costs and outcomes of treating patients aged ≥38 years with CP-CML. The efficacy parameters were synthesized from a systematic review. Utilities using the European Quality of Life-5 Dimensions tool and costs were obtained from the Thai CML population. Costs and outcomes were compared and presented as the incremental cost-effectiveness ratio in 2011 Thai baht (THB) per quality-adjusted life year (QALY) gained. One-way and probabilistic sensitivity analyses were performed to estimate parameter uncertainty. RESULTS: From a societal perspective, treatment with dasatinib was found to yield more QALYs (2.13) at a lower cost (THB 1,631,331) per person than high-dose imatinib. Nilotinib treatment was also found to be more cost-effective than high-dose imatinib, producing an incremental cost-effectiveness ratio of THB 83,328 per QALY gained. This treatment option also resulted in the highest number of QALYs gained of all of the treatment options. The costs of providing dasatinib, nilotinib, and high-dose imatinib were estimated at THB 5 billion, THB 6 billion, and THB 7 billion, respectively. CONCLUSIONS: Treatment with dasatinib or nilotinib is likely to be more cost-effective than treatment with high-dose imatinib in CP-CML patients who do not respond positively to standard-dose imatinib in the Thai context. Dasatinib was found to be more cost-effective than nilotinib.