Real-world comparison of health care costs of venetoclax-obinutuzumab vs Bruton's tyrosine kinase inhibitor use among US Medicare beneficiaries with chronic lymphocytic leukemia in the frontline setting.

BACKGROUND: Bruton's tyrosine kinase inhibitors (BTKis) and the BCL-2 inhibitor venetoclax in combination with obinutuzumab (VEN-O) are both recommended as frontline therapy in chronic lymphocytic leukemia (CLL). However, VEN-O is a 12-month fixed-duration therapy generating durable remissions whereas BTKis are continuous treat-to-progression treatments. OBJECTIVE: To examine costs before and after the fixed-duration treatment period for VEN-O relative to that observed for BTKis in a national sample of older US adults with CLL in the frontline setting. METHODS: This retrospective analysis used Medicare Parts A, B, and D claims from 2016 to 2021. Fee-for-service Medicare beneficiaries aged 66 years or older initiating frontline CLL treatment with VEN-O or a BTKi treatment between June 1, 2019, and June 30, 2020 (index date = first prescription fill date), were included in the sample. Mean cost measures were captured for both groups over 2 fixed time periods calculated from the index date: Month 0 to 12 (proxy for VEN-O on-treatment period) and Month 13 to 18 (proxy for VEN-O off-treatment period). A difference-in-difference approach was used. Multivariate generalized linear models estimated changes in adjusted mean monthly costs during Month 0 to 12 vs Month 13 to 18, for the VEN-O group relative to the BTKi group. RESULTS: The final sample contained 193 beneficiaries treated with VEN-O and 1,577 beneficiaries treated with BTKis. Risk-adjusted all-cause monthly total costs were similar for VEN-O patients ($13,887) and BTKi patients ($14,492) between Month 0 and 12. Moreover, during Month 13 to 18, the mean monthly all-cause total costs declined by 67% for VEN-O ($13,887 to $4,462) but only by 10% for BTKi ($14,492 to $13,051). Hence, the relative reduction in costs across the 2 periods was significantly larger for VEN-O (-$9,425) vs BTKi (-$1,441) patients (ie, difference in difference = -$7,984; P < 0.001). Similar patterns were observed for CLL-related costs, with the substantially larger reductions in CLL-related total monthly costs (-$9,880 VEN-O vs -$1,753 BTKi; P < 0.001) for the VEN-O group primarily driven by the larger reduction in CLL-related monthly prescription costs (-$9,437 VEN-O vs -$2,020 BTKi; P < 0.001). CONCLUSIONS: This real-world study of older adults with CLL found a large reduction in monthly Medicare costs in the 6 months after completion of the fixed-duration treatment period of VEN-O, largely driven by the reduction in CLL-related prescription drug costs. A similar decline in costs was not observed among those treated with BTKis. Our study highlights the substantial economic benefits of fixed-duration VEN-O relative to treat-to-progression therapies like BTKis in the first-line CLL setting.

Asciminib for third-line treatment of chronic myeloid leukemia: Cost-effectiveness analysis based on treatment-free remission approach. / [Artículo traducido] Asciminib para el tratamiento de la leucemia mieloide crónica en tercera línea: análisis coste-efectividad basado en el enfoque de remisión libre de tratamiento.

INTRODUCTION: The first targeted therapy in oncology, imatinib, revolutionized chronic myeloid leukemia (CML) treatment and spurred research in targeted therapies for various cancers. CML results from a chromosomal translocation, forming the BCR-ABL1 fusion gene. Asciminib has been recently approved for 3rd-line refractory or intolerant patients. Treatment-free remission (TFR) is attainable with sustained deep molecular response (DMR) and this approach could be incorporated into pharmacoeconomic models. AIMS: To establish a cost-effectiveness model comparing asciminib to approved third-generation tyrosine kinase inhibitors (TKIs) (bosutinib and ponatinib) with a focus on achieving TFR. Additionally, the budgetary impact of incorporating asciminib as a therapeutic alternative is assessed. METHODS: This model is based on a Markov chain with seven states. The condition for achieving TFR is to remain for 5 years in DMR state. Efficacy of the model was measured in QALYs, and the costs included in the base case analysis are based in Spain. A probabilistic (PSA) and deterministic analysis (DSA) were carried out to assess the variability of the model. There were achieved two independent models comparing asciminib vs. bosutinib and asciminib vs. ponatinib. RESULTS: Asciminib, when compared with ponatinib, is a cost-saving alternative, as efficacy is similar between alternatives, and asciminib has a lower cost of 30,275 €. Asciminib showed 4.33 more QALYs and a higher cost (203,591 €) than bosutinib, resulting in an ICER of €47,010.49 per QALY. PSA shows that the parameters with higher influence in the variability of the model were the probability of transitioning to BP and probabilities of achieving MMR and DMR. A one-way analysis reports that the drug cost has a higher influence on both models, and the discount rate significantly affects the asciminib vs. bosutinib model. CONCLUSION: Asciminib broadens therapeutic choices for patient's refractory or intolerant to two prior lines of treatment in a cost-effective manner. The costs of drugs significantly impact the overall cost of the disease, emphasizing the importance of the selected discount rates for each drug. Given the relatively low incidence of CML, the introduction of asciminib has a limited budgetary impact, warranting individualized decisions based on patient`s clinical characteristics.

Real-World Treatment Patterns, Survival, and Economic Burden Among Elderly MCL Patients Previously Treated With cBTKis.

BACKGROUND: While covalent Bruton's tyrosine kinase inhibitors (cBTKis) have become a standard of care treatment for relapsed/refractory mantle cell lymphoma (R/R MCL), response duration is limited and resistance to BTKi and/or adverse events develop in a subset of patients. However, little real-world evidence on post-cBTKi clinical and economic outcomes exists for these patients. PATIENTS AND METHODS: This retrospective study used 2010 to 2019 U.S. Medicare claims, to identify elderly (≥ 66 years) patients with newly-diagnosed MCL who received third-line (3L) treatment and had evidence of cBTKi use in a prior line of therapy. Outcomes were assessed ≥ 12-months post 3L-treatment initiation and included treatment patterns, all-cause and MCL-related HRU and costs, and overall survival. RESULTS: The final sample contained 230 elderly patients with R/R MCL receiving 3L treatment who had cBTKi use in a prior line of therapy (mean age 75.0, 21.7% age > 80 years; 67.4% male; 93.9% White). Common 3L treatments included chemotherapy (26.1%), lenalidomide (18.7%), and bortezomib (18.3%); 1-quarter (25.7%) of patients received a cBTKi (17.8% ibrutinib; 7.8% acalabrutinib). Overall survival was poor from 3L treatment initiation (median OS = 9.4 months; 1-years survival rate = 43.7%). Patients exhibited high rates of HRU (73.6% experienced hospitalization) and substantial costs ($145,726) in the 12-months after 3L initiation. CONCLUSION: A large unmet need exists in this patient subpopulation, highlighting the importance of ongoing development of novel therapeutics.

The cost-effectiveness of iruplinalkib versus alectinib in anaplastic lymphoma kinase-positive crizotinib-resistant advanced non-small-cell lung cancer patients in China.

Background: Iruplinalkib is a second-generation anaplastic lymphoma kinase (ALK) tyrosine kinase inhibitor (TKI) with efficacy in patients with ALK-positive crizotinib-resistant advanced non-small cell lung cancer (NSCLC), which is independently developed by a Chinese pharmaceutical company. This study examined the cost-effectiveness of iruplinalkib versus alectinib in the Chinese healthcare setting. Methods: A partitioned survival model was developed to project the economic and health outcomes. Efficacy was derived using unanchored matching-adjusted indirect comparison (MAIC). Cost and utility values were obtained from the literature and experts' opinions. Deterministic and probabilistic sensitivity analyses (PSA) were carried out to evaluate the model's robustness. Results: Treatment with iruplinalkib versus alectinib resulted in a gain of 0.843 quality-adjusted life years (QALYs) with incremental costs of $20,493.27, resulting in an incremental cost-effectiveness ratio (ICER) of $24,313.95/QALY. Parameters related to relative efficacy and drug costs were the main drivers of the model outcomes. From the PSA, iruplinalkib had a 90% probability of being cost-effective at a willingness-to-pay threshold of $37,863.56/QALY. Conclusion: Compared to alectinib, iruplinalkib is a cost-effective therapy for patients with ALK-positive crizotinib-resistant advanced NSCLC.

Asciminib for third-line treatment of chronic myeloid leukemia: Cost-effectiveness analysis based on treatment-free remission approach.

INTRODUCTION: The first targeted therapy in oncology, imatinib, revolutionized chronic myeloid leukemia (CML) treatment and spurred research in targeted therapies for various cancers. CML results from a chromosomal translocation, forming the BCR-ABL1 fusion gene. Asciminib has been recently approved for third-line refractory or intolerant patients. Treatment-free remission (TFR) is attainable with sustained deep molecular response (DMR) and this approach could be incorporated into pharmacoeconomic models. AIMS: To establish a cost-effectiveness model comparing asciminib to approved third-generation tyrosine kinase inhibitors (TKIs) (bosutinib and ponatinib) with a focus on achieving TFR. Additionally, the budgetary impact of incorporating asciminib as a therapeutic alternative is assessed. METHODS: This model is based on a Markov chain with 7 states. The condition for achieving TFR is to remain for 5 years in DMR state. Efficacy of the model was measured in QALYs, and the costs included in the base case analysis are based in Spain. A probabilistic (PSA) and deterministic analysis (DSA) were carried out to assess the variability of the model. There were achieved 2 independent models comparing asciminib vs bosutinib and asciminib vs ponatinib. RESULTS: Asciminib, when compared with ponatinib, is a cost-saving alternative, as efficacy is similar between alternatives, and asciminib have a lower cost of 30,275€. Asciminib showed 4.33 more QALYs and a higher cost (203,591€) than bosutinib, resulting in an ICER of €47,010.49 per QALY. PSA shows that the parameters with higher influence in the variability of the model were the probability of transitioning to BP and probabilities of achieving MMR and DMR. A one-way analysis reports that the drug cost has a higher influence on both models, and the discount rate significantly affects the asciminib vs bosutinib model. CONCLUSION: Asciminib broadens therapeutic choices for patient's refractory or intolerant to 2 prior lines of treatment in a cost-effectiveness manner. The costs of drugs significantly impact the overall cost of the disease, emphasizing the importance of the selected discount rates for each drug. Given the relatively low incidence of CML, the introduction of asciminib has a limited budgetary impact, warranting individualized decisions based on patient`s clinical characteristics.

Real-World Health Care Resource Use and Costs Among Patients With Chronic Lymphocytic Leukemia Treated With Venetoclax-Based and Bruton Tyrosine Kinase Inhibitor-Based Regimens in the Second-Line Setting.

PURPOSE: Real-world evidence comparing health care resource use (HRU) and costs between novel targeted therapies among patients with chronic lymphocytic leukemia (CLL) is lacking. We compared all-cause and CLL-specific HRU and costs between patients initiated on B-cell lymphoma 2 inhibitor (venetoclax)- or Bruton tyrosine kinase inhibitor (BTKi)-based regimens in the second-line (2L) setting. METHODS: This is a retrospective observational study using Optum Clinformatics Data Mart of adult patients with CLL/small lymphocytic lymphoma who received 2L venetoclax- or BTKi-based regimens (January 2018-December 2021) for the first time and had ≥one CLL diagnostic claim after 2L initiation and ≥two claims for venetoclax or BTKi. Baseline characteristics were balanced using stabilized inverse probability of treatment weights. Mean monthly cost difference (MMCD) between cohorts for all-cause and CLL-specific per patient per month (PPPM) costs was estimated. Rates of PPPM-HRU were compared between cohorts using rate ratios (RRs). RESULTS: Of 280 patients, median age 75.5 years, 64.6% and 35.4% received BTKi- versus venetoclax-based regimens, respectively. Most BTKi-treated patients received monotherapy (88.4%), whereas 62.3% of venetoclax-treated patients received combination therapy with anti-CD20 agents. The median duration of 2L therapy was 11.6 and 11.0 months for BTKi versus venetoclax cohorts, respectively. All-cause total costs were lower for venetoclax versus BTKi (MMCD [SE], $-2,497.64 [$1,006.77] in US dollars (USD); P = .01), driven by lower medication costs offsetting medical costs; trends were similar for CLL-specific estimates. Outpatient HRU was higher for venetoclax versus BTKi (RR all-cause: 1.22 versus CLL-specific: 1.64). CONCLUSION: Venetoclax was associated with total monthly cost savings versus BTKis, illustrating the economic value of time-limited venetoclax-based regimens in the 2L setting.

Cost-effectiveness of adding quizartinib to induction chemotherapy for patients with FLT3-mutant acute myeloid leukemia.

The FLT3 inhibitor quizartinib has been shown to improve overall survival when added to intensive induction chemotherapy ("7 + 3") in patients 18-75 years old with newly diagnosed AML harboring a FLT3-ITD mutation. However, the health economic implications of this approval are unknown. We evaluated the cost-effectiveness of quizartinib using a partitioned survival analysis model. One-way and probabilistic sensitivity analyses were conducted. In the base case scenario, the addition of quizartinib to 7 + 3 resulted in incremental costs of $289,932 compared with 7 + 3 alone. With an incremental gain of 0.84 quality-adjusted life years (QALYs) with quizartinib + 7 + 3 induction vs. 7 + 3 alone, the incremental cost-effectiveness ratio for the addition of quizartinib to standard 7 + 3 was $344,039/QALY. Only an 87% reduction in the average wholesale price of quizartinib or omitting quizartinib continuation therapy after completion of consolidation therapy and allogeneic hematopoietic cell transplant would make quizartinib a cost-effective option.

Critical Examination of Modeling Approaches Used in Economic Evaluations of First-Line Treatments for Locally Advanced or Metastatic Non-Small Cell Lung Cancer Harboring Epidermal Growth Factor Receptor Mutations: A Systematic Literature Review.

BACKGROUND: Non-small cell lung cancer (NSCLC) is the most common type of lung cancer, with up to 32% of patients with NSCLC harboring an epidermal growth factor receptor (EGFR) mutation. NSCLC harboring an EGFR mutation has a dedicated treatment pathway, with EGFR tyrosine kinase inhibitors and platinum-based chemotherapy often being the therapy of choice. OBJECTIVE: The aim of this study was to systemically review and summarize economic models of first-line treatments used for locally advanced or metastatic NSCLC harboring EGFR mutations, as well as to identify areas for improvement for future models. METHODS: Literature searches were conducted via Ovid in PubMed, MEDLINE, MEDLINE In-Process, Embase, Evidence-Based Medicine Reviews: Health Technology Assessment, Evidence-Based Medicine Reviews: National Health Service Economic Evaluation Database, and EconLit. An initial search was conducted on 19 December 2022 and updated on 11 April 2023. Studies were selected according to predefined criteria using the Population, Intervention, Comparator, Outcome and Study design (PICOS) framework. RESULTS: Sixty-seven articles were included in the review, representing 59 unique studies. The majority of included models were cost-utility analyses (n = 52), with the remaining studies being cost-effectiveness analyses (n = 4) and a cost-minimization analysis (n = 1). Two studies incorporated both a cost-utility and cost-minimization analysis. Although the model structure across studies was consistently reported, justification for this choice was often lacking. CONCLUSIONS: Although the reporting of economic models in NSCLC harboring EGFR mutations is generally good, many of these studies lacked sufficient reporting of justification for structural choices, performing extensive sensitivity analyses and validation in economic evaluations. In resolving such gaps, the validity of future models can be increased to guide healthcare decision making in rare indications.

A systematic review of economic evaluations of tyrosine kinase inhibitors for non-small cell lung cancer (NSCLC).

INTRODUCTION: Although tyrosine kinase inhibitors (TKIs) have improved the efficacy of treatment for non-small cell lung cancer (NSCLC), the accessibility of TKIs is limited due to high costs. Despite the critical role of the cost-effectiveness of TKIs on decision-making, no systematic reviews have compared the cost-effectiveness of comparable TKIs. Therefore, we systemically reviewed the economic evaluation studies on various TKIs for NSCLC. AREAS COVERED: We searched PubMed and the Cochran Library to identify the published economic evaluation studies of TKIs in NSCLC patients that were published by January 2022. All of the included studies (n = 38) evaluated the cost-effectiveness of epidermal growth factor receptor (EGFR)-TKIs (n = 29) or anaplastic lymphocyte kinase (ALK)-TKIs (n = 9). The cost-effectiveness results were reported as the incremental cost-effectiveness ratio per quality-adjusted life-year, except for three studies. EXPERT OPINION: We found that the economic evaluation studies of the first and second generation of EGFR-TKIs and ALK-TKIs varied by the country and study settings, such as comparator and input parameters. In 12 studies, osimertinib (EGFR-TKI) was not cost-effective compared to other first/second EGFR-TKIs, regardless of the study settings. More evidence can be provided about cost-effectiveness of the third-generation TKIs in future research.

Optimal treatment sequence for targeted immune modulators for the treatment of moderate to severe ulcerative colitis.

BACKGROUND: Ulcerative colitis is a chronic immune-mediated inflammatory condition of the large intestine and rectum. Several targeted immune modulators (TIMs) have demonstrated effectiveness for the treatment of moderate to severe ulcerative colitis and are approved by the FDA. Patients may try multiple TIMs, and currently there are no biomarkers or prognostic factors to guide choice of treatment sequence. In 2020, the Institute for Clinical and Economic Review (ICER) conducted a review of TIMs for the treatment of ulcerative colitis as individual agents relative to conventional treatment but did not address the relative ranking of various treatment sequences to each other. OBJECTIVE: To extend the ICER framework to identify the optimal treatment sequence as informed by metrics such as maximizing incremental net health benefit (NHB), minimizing incremental total cost, or maximizing incremental quality-adjusted life-years (QALYs). METHODS: The model was developed as a Markov model with 8-week cycles over a lifetime time horizon from a US payer perspective, including only direct health care costs. Health states consisted of active moderate to severe ulcerative colitis, clinical response without achieving remission, clinical remission, and death. Efficacy of TIMs were informed by the ICER-conducted network meta-analysis. Up to 3 treatments were modeled in a sequence that consisted of 2 different TIMs followed by conventional treatment. Sequences were ranked according to each objective. NHB was calculated using a threshold of $150,000 per QALY gained. Probabilistic sensitivity analysis (PSA) was undertaken to estimate the probability of each sequence having the highest NHB rank under each objective. RESULTS: 21 possible sequences were evaluated in the base case. Two attempts at conventional treatment represented the lowest cost option and, while yielding the fewest QALYs, resulted in the highest NHB. None of the sequences had an incremental cost per QALY below $150,000 relative to 2 attempts with conventional treatment, so the resulting NHB was negative for all sequences. The sequence with the highest NHB was infliximab-dyyb followed by tofacitinib (-0.116). This regimen also had the lowest incremental costs ($37,266). For orally and subcutaneously administered TIMs, the sequence of golimumab-tofacitinib had the highest NHB (-0.344). Ustekinumab-vedolizumab was the top-ranked sequence as measured by QALY maximization (0.172 incremental QALYs) but also had the highest total incremental cost ($166,094). Results of the PSA were consistent with deterministic rankings for the top-ranking sequences but also showed that the top 2 or 3 regimens were often close together. CONCLUSIONS: Based on the results of this analysis, the optimal sequence of TIMs as measured by NHB and cost minimization was infliximab or biosimilars as first-line treatment, then moving to tofacitinib, adalimumab, or vedolizumab. Sequences that generated the most QALYs began with ustekinumab, followed by vedolizumab, tofacitinib, and adalimumab. DISCLOSURES: This study was based on an evidence synthesis and economic evaluation sponsored by the Institute for Clinical and Economic Review (ICER). Pandey and Fazioli are employees of ICER. Bloudek reports grants from ICER during the conduct of the study and personal fees from Astellas, Akcea, Dermira, GlaxoSmithKline, Sunovion, Seattle Genetics, and TerSera Therapeutics, outside the submitted work. Pandey reports grants from California Healthcare Foundation, Harvard Pilgrim Healthcare, Kaiser Foundation Health Plan Inc., and the Donoghue Foundation, during the conduct of the study, and other support from Aetna, America's Health Insurance Plans, Anthem, AbbVie, Alnylam, AstraZeneca, Biogen, Genentech/Roche, GlaxoSmithSline, Harvard Pilgrim, Health Care Service Corporation, Health Partners, Johnson & Johnson (Janssen), Kaiser Permanente, LEO Pharma, Mallinckrodt, Merck, Novartis, National Pharmaceutical Council, Premera, Prime Therapeutics, Regeneron, Sanofi, Spark Therapeutics, United Healthcare, HealthFirst, Pfizer, Boehringer-Ingelheim, uniQure, Evolve Pharmacy Solutions, and Humana, outside the submitted work. Fazioli reports grants from Arnold Ventures, California Healthcare Foundation, Harvard Pilgrim Healthcare, Kaiser Foundation Health Plan Inc., and The Donaghue Foundation, during the conduct of the study, and other support from Aetna, America's Health Insurance Plans, Anthem, AbbVie, Alnylam, AstraZeneca, Biogen, Blue Shield of CA, Cambia Health Services, CVS, Editas, Express Scripts, Genentech/Roche, GlaxoSmithKline, Harvard Pilgrim, Health Care Service Corporation, Health Partners, Johnson & Johnson (Janssen), Kaiser Permanente, LEO Pharma, Mallinckrodt, Merck, Novartis, National Pharmaceutical Council, Premera, Prime Therapeutics, Regeneron, Sanofi, Spark Therapeutics, United Healthcare, HealthFirst, Pfizer, Boehringer-lngelheim, uniQure, Evolve Phamacy Solutions, and Humana, outside the submitted work. Ollendorf reports grants from ICER, during the conduct of the study, along with other support from CEA Registry sponsors and personal fees from EMD Serono, Amgen, Analysis Group, Aspen Institute/University of Southern California, GalbraithWight, Cytokinetics, Sunovion, University of Colorado, Center for Global Development, and Neurocrine, outside the submitted work. Carlson reports grants from ICER, during the conduct of the study, and personal fees from Allergan, outside the submitted work. The inputs and model framework that were leveraged for this analysis were presented as part of the ICER assessment of TIMs for the treatment of moderate to severe ulcerative colitis.

Therapeutic Advances in the Management of Patients with Advanced RET Fusion-Positive Non-Small Cell Lung Cancer.

OPINION STATEMENT: Screening for activating driver gene alterations at the time of diagnosis is the standard of care for advanced non-small cell lung cancer (NSCLC). Activating RET fusions are identified in approximately 1-2% of NSCLCs and have emerged as a targetable driver alteration. Selpercatinib and pralsetinib are RET-selective tyrosine kinase inhibitors (TKIs) with encouraging efficacy, intracranial activity, and tolerability that we recommend as first-line therapy. As with use of TKIs in other oncogene-addicted NSCLCs, development of acquired resistance is pervasive and should be specifically delineated through use of repeat tissue biopsy with genetic profiling at the time of disease progression. If an actionable resistance mechanism emerges for which there is a candidate targeted therapy, combination inhibition should be considered. Alternatively, or in the absence of such findings, platinum doublet chemotherapy or particularly platinum-pemetrexed therapy with or without bevacizumab demonstrates a moderate effect.We would not recommend the routine use of nonselective multi-targeted TKIs such as cabozantinib and vandetanib, which have modest activity but limited tolerability due to predictable off-target effects. Single-agent immunotherapy has minimal activity in RET fusion-positive NSCLC. The role of combination chemotherapy and immunotherapy requires further study but may be considered, particularly in the presence of an activating KRAS alteration. While further development of novel RET-selective TKIs may address common RET-specific resistance mutations, they will not have activity against off-target, RET-independent resistance mechanisms. This again highlights the importance of serial biopsy and next-generation sequencing for the rational choice of sequential therapy in RET fusion-positive NSCLC.

Budget Impact of Tyrosine Kinase Inhibitor Discontinuation in Chronic Myeloid Leukemia With Sustained Deep Molecular Response.

OBJECTIVES: Tyrosine kinase inhibitors (TKIs) account for the vast majority of healthcare expenditure on patients with chronic myeloid leukemia (CML), and it has been demonstrated that TKI discontinuation in patients in long-term deep molecular remission (DMR) is safe and improves quality of life. Our objective was to estimate the budget impact of TKI discontinuation in CML patients in long-term DMR from the perspective of the French healthcare system. METHODS: This analysis was conducted over a 5-year time horizon using a Markov model with cycles of 6 months. Transition probabilities were estimated through systematic reviews and meta-analyses. Costs were estimated from the French National Claims Database. Monte Carlo simulations were performed to take into account the uncertainty surrounding model parameters. Sensitivity analyses were carried out by varying the size of the target population and the cost of TKIs. RESULTS: Over a 5-year period and for a target population of 100 patients each year eligible and agreeing to stop TKI, the TKI discontinuation strategy would save €25.5 million (95% confidence interval -39.3 to 70.0). In this model, the probability that TKI discontinuation would be more expensive than TKI continuation was 12.0%. In sensitivity analyses, mean savings ranged from €14.9 million to €62.9 million. CONCLUSIONS: This study provides transparent, reproducible, and interpretable results for healthcare professionals and policy makers. Our results clearly show that innovative healthcare strategies can benefit both the healthcare system and patients. Savings from generalizing TKI discontinuation in CML patients in sustained DMR should yield health gains for other patients.

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.

Interventions to Improve Adherence to Tyrosine Kinase Inhibitors in Chronic Myeloid Leukemia: A Systematic Review.

BACKGROUND: Lack of adherence to tyrosine kinase inhibitors (TKIs) is a significant problem resulting in incomplete cytogenetic response and increased mortality in patients with chronic myeloid leukemia (CML). Few studies have been conducted on interventions to improve adherence. The authors conducted a systematic review to explore studies that examined the impact of strategies to improve TKI adherence among individuals with CML. METHODS: The first 2 authors completed a systematic literature review according to the guidelines in Preferred Reporting Items for Systematic Review and Meta-Analysis (PRISMA). Studies (n=2633) conducted between 1980 and 2019 were identified through 3 databases and examined for inclusion/exclusion criteria. RESULTS: Fourteen studies were identified which met the eligibility criteria. The studies only examined adherence to imatinib, dasatinib, or nilotinib. Ten of the 14 used large data sets (commercial health insurance plans or Surveillance Epidemiology and End Results [SEER] data) for analysis. The majority of the studies used a cohort design. Adherence was defined and measured in a variety of ways with most studies using 80% or higher as adequate adherence. Strategies not focused on health care costs used a multidisciplinary team approach. CONCLUSION: Development of evidence to improve treatment adherence to TKIs for CML have relied on large data sets rather than prospective trials. Current studies lack patient focused interventions.

Cost-effectiveness analysis of first-line treatments for advanced epidermal growth factor receptor-mutant non-small cell lung cancer patients.

OBJECTIVES: Recent studies showed prolonged survival for advanced epidermal growth factor receptor (EGFR)-mutant non-small cell lung cancer (NSCLC) patients treated with both monotherapies and combined therapies. However, high costs limit clinical applications. Thus, we conducted this cost-effectiveness analysis to explore an optimal first-line treatment for advanced EGFR-mutant NSCLC patients. MATERIALS AND METHODS: Survival data were extracted from six clinical trials, including ARCHER1050 (dacomitinib vs. gefitinib); FLAURA (osimertinib vs. gefitinib/erlotinib); JO25567 and NEJ026 (bevacizumab +erlotinib vs. erlotinib); NEJ009 (gefitinib +chemotherapy vs. gefitinib); and NCT02148380 (gefitinib +chemotherapy vs. gefitinib vs. chemotherapy) trials. Cost-related data were obtained from hospitals and published literature. The effect parameter (quality-adjusted life year [QALY]) was the reflection of both survival and utility. Incremental cost-effectiveness ratio (ICER), average cost-effectiveness ratio (ACER), and net benefit were calculated, and the willingness-to-pay (WTP) threshold was set at $30828/QALY from the perspective of the Chinese healthcare system. Sensitivity analysis was performed to explore the stability of results. RESULTS: We compared treatment groups with control groups in each trial. ICERs were $1897750.74/QALY (ARCHER1050), $416560.02/QALY (FLAURA), -$477607.48/QALY (JO25567), -$464326.66/QALY (NEJ026), -$277121.22/QALY (NEJ009), -$399360.94/QALY (gefitinib as comparison, NCT02148380), and -$170733.05/QALY (chemotherapy as comparison, NCT02148380). Moreover, ACER and net benefit showed that the combination of EGFR-TKI with chemotherapy and osimertinib was of more economic benefit following first-generation EGFR-TKIs. Sensitivity analyses showed that the impact of utilities and monotherapy could be cost-effective with a 50% cost reduction. CONCLUSION: First-generation EGFR-TKI therapy remained the most cost-effective treatment option for advanced EGFR-mutant NSCLC patients. Our results could serve as both a reference for both clinical practice and the formulation of medical insurance reimbursement.

Upfront Management of ALK-Rearranged Metastatic Non-small Cell Lung Cancer: One Inhibitor Fits All?

PURPOSE OF REVIEW: Anaplastic lymphoma kinase (ALK) rearrangements represent a seldom event in non-small cell lung cancer (NSCLC). Given the oncogene alteration, ALK targeting represents the main therapeutic strategy. Here, we review evidence regarding ALK inhibitors (ALKi): clinical activity, safety profiles, financial costs, and biomarkers of efficacy. RECENT FINDINGS: During the past 10 years, multiple ALKi have been developed, and four different compounds are currently available as upfront options for ALK+ NSCLC patients: crizotinib, ceritinib, alectinib, and brigatinib. Second-generation (2G) ALKi demonstrated superior clinical activity in terms of median progression-free survival (mPFS), objective response rate (ORR), intracranial disease control, and duration of response (DOR) when compared with crizotinib. 2G ALKi represent the current gold-standard first-line treatment for ALK-rearranged metastatic NSCLC. Among all available options, in our opinion, alectinib has likely the best profile of clinical activity and safety, thus emerging as the best upfront therapy. More insights will come from ongoing trials and analysis of biomarkers.

The costs of treating and not treating patients with chronic myeloid leukemia with tyrosine kinase inhibitors among Medicare patients in the United States.

BACKGROUND: Patients with high cost-sharing of tyrosine kinase inhibitors (TKIs) experience delays in treatment for chronic myeloid leukemia (CML). To the authors' knowledge, the clinical outcomes among and costs for patients not receiving TKIs are not well defined. METHODS: Using the Surveillance, Epidemiology, and End Results (SEER)-Medicare database, the authors evaluated differences in TKI initiation, health care use, cost, and survival among patients with CML with continuous Medicare Parts A and B and Part D coverage who were diagnosed between 2007 and 2015. RESULTS: A total of 941 patients were included. Approximately 29% of all patients did not initiate treatment with TKIs within 6 months (non-TKI users), and had lower rates of BCR-ABL testing and more hospitalizations compared with TKI users. Approximately 21% were not found to have any TKI claims at any time. TKI initiation rates within 6 months of diagnosis increased for all patients over time (61% to 85%), with greater improvements observed in patients receiving subsidies (55% to 90%). Total Medicare costs were greater in patients treated with TKIs, with approximately 50% because of TKI costs. Non-TKI users had more inpatient costs compared with TKI users. Trends in cost remained significant when adjusting for age and comorbidities. The median overall survival was 40 months (95% confidence interval [95% CI], 34-48 months) compared with 86 months (95% CI, 73 months to not reached), respectively, for non-TKI users versus TKI users, a finding that remained consistent when adjusting for age, comorbidities, and subsidy status (hazard ratio, 2.23; 95% CI, 1.77-2.81). CONCLUSIONS: Approximately 21% of all patients with CML did not receive TKIs at any time. Cost-sharing subsidies consistently are found to be associated with higher initiation rates. Non-TKI users had higher inpatient costs and poorer survival outcomes. Interventions to lower TKI costs for all patients are desirable.

Continuation of Anti-TNF in Patients With Ulcerative Colitis in Remission Is Not Cost-effective Compared With Treatment Withdrawal: A Markov Model.

BACKGROUND AND AIMS: Anti-tumour necrosis factor alpha [anti-TNF] treatment accounts for 31% of health care expenditures associated with ulcerative colitis [UC]. Withdrawal of anti-TNF in patients with UC in remission may decrease side effects and infections, while promoting cost containment. Approximately 36% of patients relapse within 12-24 months of anti-TNF withdrawal, but reintroduction of treatment is successful in 80% of patients. We aimed to evaluate the cost-effectiveness of continuation versus withdrawal of anti-TNF in patients with UC in remission. METHODS: We developed a Markov model comparing cost-effectiveness of anti-TNF continuation versus withdrawal, from a health care provider perspective. Transition probabilities were calculated from literature, or estimated by an expert panel of 11 gastroenterologists. Deterministic and probabilistic sensitivity analyses were performed to account for assumptions and uncertainty. The cost-effectiveness threshold was set at an incremental cost-effectiveness ratio of €80,000 per quality-adjusted life-year [QALY]. RESULTS: At 5 years, anti-TNF withdrawal was less costly [-€10,781 per patient], but also slightly less effective [-0.04 QALY per patient] than continued treatment. Continuation of anti-TNF compared with withdrawal costs €300,390/QALY, exceeding the cost-effectiveness threshold. Continued therapy would become cost-effective if the relapse rate following anti-TNF withdrawal was ≥43% higher, or if adalimumab or infliximab [biosimilar] prices fell below €87/40 mg and €66/100 mg, respectively. CONCLUSIONS: Continuation of anti-TNF in UC patients in remission is not cost-effective compared with withdrawal. A stop-and-reintroduction strategy is cost-saving but is slightly less effective than continued therapy. This strategy could be improved by identifying patients at increased risk of relapse.