scholarly journals First-Line Atezolizumab Plus Bevacizumab versus Sorafenib in Hepatocellular Carcinoma: A Cost-Effectiveness Analysis

Cancers ◽  
2021 ◽  
Vol 13 (5) ◽  
pp. 931
Author(s):  
Chi-Leung Chiang ◽  
Sik-Kwan Chan ◽  
Shing-Fung Lee ◽  
Horace Cheuk-Wai Choi

Background: The IMbrave 150 trial revealed that atezolizumab plus bevacizumab (atezo–bev) improves survival in patients with unresectable hepatocellular carcinoma (HCC) (1 year survival rate: 67.2% vs. 54.6%). We assessed the cost-effectiveness of atezo–bev vs. sorafenib as first-line therapy in patients with unresectable HCC from the US payer perspective. Methods: Using data from the IMbrave 150, we developed a Markov model to compare the lifetime cost and efficacy of atezo–bev as first-line systemic therapy in HCC with those of sorafenib. The main outcomes were life-years, quality-adjusted life-years (QALYs), lifetime costs, and incremental cost-effectiveness ratio (ICER). Results: Atezo–bev demonstrated a gain of 0.44 QALYs, with an additional cost of USD 79,074. The ICER of atezo–bev was USD 179,729 per QALY when compared with sorafenib. The model was most sensitive to the overall survival hazard ratio and body weight. If we assumed that all patients at the end of the IMbrave 150 trial were cured of HCC, atezo–bev was cost-effective (ICER USD 53,854 per QALY). However, if all patients followed the Surveillance, Epidemiology, and End Results data, the ICER of atezo–bev was USD 385,857 per QALY. Reducing the price of atezo–bev by 20% and 29% would satisfy the USD 150,000/QALY and 100,000/QALY willingness-to-pay threshold. Moreover, capping the duration of therapy to ≤12 months or reducing the dosage of bev to ≤10 mg/kg would render atezo–bev cost-effective. Conclusions: The long-term effectiveness of atezo–bev is a critical but uncertain determinant of its cost-effectiveness. Price reduction would favorably influence cost-effectiveness, even if long-term clinical outcomes were modest. Further studies to optimize the duration and dosage of therapy are warranted.

2022 ◽  
Vol 12 ◽  
Author(s):  
Qiao Liu ◽  
Zhen Zhou ◽  
Xia Luo ◽  
Lidan Yi ◽  
Liubao Peng ◽  
...  

Objective To compare the cost-effectiveness of the combination of pembrolizumab and chemotherapy (Pembro+Chemo) versus pembrolizumab monotherapy (Pembro) as the first-line treatment for metastatic non-squamous and squamous non-small-cell lung cancer (NSCLC) with PD-L1expression ≥50%, respectively, from a US health care perspective.Material and Methods A comprehensive Makrov model were designed to compare the health costs and outcomes associated with first-line Pembro+Chemo and first-line Pembro over a 20-years time horizon. Health states consisted of three main states: progression-free survival (PFS), progressive disease (PD) and death, among which the PFS health state was divided into two substates: PFS while receiving first-line therapy and PFS with discontinued first-line therapy. Two scenario analyses were performed to explore satisfactory long-term survival modeling.Results In base case analysis, for non-squamous NSCLC patients, Pembro+Chemo was associated with a significantly longer life expectancy [3.24 vs 2.16 quality-adjusted life-years (QALYs)] and a substantially greater healthcare cost ($341,237 vs $159,055) compared with Pembro, resulting in an ICER of $169,335/QALY; for squamous NSCLC patients, Pembro+Chemo was associated with a slightly extended life expectancy of 0.22 QALYs and a marginal incremental cost of $3,449 compared with Pembro, resulting in an ICER of $15,613/QALY. Our results were particularly sensitive to parameters that determine QALYs. The first scenario analysis yielded lower ICERs than our base case results. The second scenario analysis founded Pembro+Chemo was dominated by Pembro.Conclusion For metastatic non-squamous NSCLC patients with PD-L1 expression ≥50%, first-line Pembro+Chemo was not cost-effective when compared with first-line Pembro. In contrast, for the squamous NSCLC patient population, our results supported the first-line Pembro+Chemo as a cost-effective treatment. Although there are multiple approaches that are used for extrapolating long-term survival, the optimal method has yet to be determined.


2019 ◽  
Author(s):  
Ching-Yu Wang ◽  
Phuong N. Pham ◽  
Sarah Kim ◽  
Karthik Lingineni ◽  
Stephan Schmidt ◽  
...  

ABSTRACTGeneric entry of newer anticoagulants is expected to decrease the costs of atrial fibrillation management. However, when making switches between brand and generic medications, bioequivalence failures are possible. The objectives of this study were to predict and compare the lifetime cost-effectiveness of brand dabigatran with hypothetical future generics. Markov micro-simulations were modified to predict the lifetime costs and quality-adjusted life years of patients on either brand or generic dabigatran from a U.S. private payer perspective. Event rates for generics were predicted using previously developed pharmacokinetic-pharmacodynamic models. The analyses showed that generic dabigatran with lower-than-brand systemic exposure was dominant. Meanwhile, generic dabigatran with extremely high systemic exposure was not cost-effective compared to the brand reference. Cost-effectiveness of generic medications cannot always be assumed as shown in this example. Combined use of pharmacometric and pharmacoeconomic models can assist in decision making between brand and generic pharmacotherapies.


2021 ◽  
Vol 39 (3_suppl) ◽  
pp. 295-295 ◽  
Author(s):  
Wenjun Wang ◽  
Jingjing Wang ◽  
Xin Zhang ◽  
Yikai Wang ◽  
Juanjuan Shi ◽  
...  

295 Background: In May 2020, atezolizumab plus bevacizumab was approved by US Food and Drug Administration for patients with unresectable or metastatic hepatocellular carcinoma (HCC) who have not received prior systemic therapy due to improvement in overall and progression-free survival compared with standard sorafenib treatment. However, because of the high cost of atezolizumab plus bevacizumab, there is a need to assess its value by considering both efficacy and cost. The aim of this study is to evaluate the cost-effectiveness of atezolizumab plus bevacizumab vs sorafenib for patients with unresectable or metastatic HCC from the US payer perspective. Methods: A partitioned-survival model was developed to compare health care costs and clinical outcomes of atezolizumab plus bevacizumab vs sorafenib in first-line treatment of unresectable or metastatic HCC over 6-year horizon. Treatment effects were extracted from the IMbrave150 trial. Health care cost and health utility data were obtained from published studies and databases. Incremental cost-effectiveness ratio (ICER) was calculated as the ratio of the incremental cost to the incremental quality-adjusted life years (QALYs). One-way deterministic and probabilistic sensitivity analyses were used to examine model uncertainty. Additional subgroup analyses were performed. Results: Atezolizumab plus bevacizumab resulted in increase of 0.623 life-years, 0.484 QALYs and $158,781 per patient at the base case analysis. The ICER was $322,500 per QALY (95% confidence interval, $136,275 to $801,509 per QALY), with 0.5% and 4.1% chance of being cost-effective at a willingness-to-pay threshold of $100,000 and $150,000 per QALY, respectively. The ICER never went below $150,000 per QALY in the one-way sensitivity analyses and among patients of clinically relevant subgroups in the subgroup analyses. Conclusions: Atezolizumab plus bevacizumab is unlikely to be cost-effective compared with sorafenib in first-line treatment of patients with unresectable or metastatic HCC from the US payer perspective.


2021 ◽  
Vol 39 (15_suppl) ◽  
pp. e21104-e21104
Author(s):  
Nimer S. Alkhatib ◽  
Briana Choi ◽  
Hala Halawah ◽  
Matthias Calamia ◽  
Dexter Gulick ◽  
...  

e21104 Background: Crizotinib, alectinib, ceritinib, and brigatinib are approved as second line treatment for ALK+ NSCLC. Crizotinib was the first ALK inhibitor for first line therapy approved by Food and Drug Administration (2011) then ceritinib (2014), alectinib (2015), and brigatinib (2017) were approved as second line drugs. Following more data, these agents were approved as the first line therapy (2017 for ceritinib and alectinib; 2020 for brigatinib). These remain as a treatment option in patients who fail the first line therapy. Cost-effectiveness/utility analyses were conducted to assess clinical efficacy with varying costs of the agents. Methods: A three state Markov model were assumed (progression free, progression and death). Progression free survival (PFS) curves were digitized and fitted with exponential function. US payer perspective, a lifetime horizon, and discount rate of 3% were applied. Drug costs were Redbook wholesale acquisition cost. Other costs included were monitoring, adverse events and disease progression from published data (US$ 2020). Adverse events reported >5% in patients were included. Measured outcomes were PFS life years (PFSLY) and quality adjusted life years (PFSQALY). Crizotinib was the reference drug. Incremental cost-effectiveness and utility ratios (ICER/ICUR) of PFSLY and PFSQALY gained (PFSLYG, PFSQALYG) and lost were estimated. Base case (BCA) and probabilistic sensitivity analyses (PSA) were conducted. Results: Crizotinib was the reference drug for the following outcomes. For alectinib, with the decremental cost of -$14,653 (-$14,712), the incremental PFSLY of 0.16 (0.16) and PFSQALY of 0.05 (0.05) resulted in an ICER / PFSLYG of -$89,337 (-$88,604) and an ICUR / PFSQALYG of -$269,835 (-$266,510). For brigatinib, with the decremental cost of -$14,975 (-$14,954), the incremental PFSLY of 0.01 (0.01) and PFSQALY of ̃0.01 (0.02) yielded an ICER / PFSLYG of -$1,982,962 (-$1,431,631) and an ICUR / PFSQALYG of -$2,140,534 (-$570,538). For ceritinib, with the incremental cost of $7,590 ($7,514), there were decremental PFSLY of -0.01 (-0.01) and PFSQALY of -0.03 (-0.03). Conclusions: As second line treatment, crizotinib, ceritinib, and brigatinib had comparable PFSLYs and PFSQALYs while alectinib had the most PFSLY and PFSQALY and the lowest cost. Therefore, alectinib is the most cost-effective treatment for treating ALK+ NSCLC as the second line therapy.[Table: see text]


2020 ◽  
Vol 9 (8) ◽  
pp. 553-562
Author(s):  
Hongfu Cai ◽  
Longfeng Zhang ◽  
Na Li ◽  
Bin Zheng ◽  
Maobai Liu

Aim: To investigate the cost–effectiveness of lenvatinib and sorafenib in the treatment of patients with nonresected hepatocellular carcinoma in China. Materials & methods: Markov model was used to simulate the direct medical cost and quality-adjusted life years (QALY) of patients with hepatocellular carcinoma. Clinical data were derived from the Phase 3 randomized clinical trial in a Chinese population. Results: Sorafenib treatment resulted in 1.794 QALYs at a cost of $43,780.73. Lenvatinib treatment resulted in 2.916 QALYs for patients weighing <60 and ≥60 kg at a cost of $57,049.43 and $75,900.36, The incremental cost–effectiveness ratio to the sorafenib treatment group was $11,825.94/QALY and $28,627.12/QALY, respectively. Conclusion: According to WHO’s triple GDP per capita, the use of lenvatinib by providing drugs is a cost-effective strategy.


2020 ◽  
Vol 9 (6) ◽  
pp. 1664 ◽  
Author(s):  
Tristan M. Snowsill ◽  
Neil A. J. Ryan ◽  
Emma J. Crosbie

Lynch syndrome (LS) is a hereditary cancer syndrome responsible for 3% of all endometrial cancer and 5% in those aged under 70 years. It is unclear whether universal testing for LS in endometrial cancer patients would be cost-effective. The Manchester approach to identifying LS in endometrial cancer patients uses immunohistochemistry (IHC) to detect mismatch repair (MMR) deficiency, incorporates testing for MLH1 promoter hypermethylation, and incorporates genetic testing for pathogenic MMR variants. We aimed to assess the cost-effectiveness of the Manchester approach on the basis of primary research data from clinical practice in Manchester. The Proportion of Endometrial Tumours Associated with Lynch Syndrome (PETALS) study informed estimates of diagnostic performances for a number of different strategies. A recent microcosting study was adapted and was used to estimate diagnostic costs. A Markov model was used to predict long-term costs and health outcomes (measured in quality-adjusted life years, QALYs) for individuals and their relatives. Bootstrapping and probabilistic sensitivity analysis were used to estimate the uncertainty in cost-effectiveness. The Manchester approach dominated other reflex testing strategies when considering diagnostic costs and Lynch syndrome cases identified. When considering long-term costs and QALYs the Manchester approach was the optimal strategy, costing £5459 per QALY gained (compared to thresholds of £20,000 to £30,000 per QALY commonly used in the National Health Service (NHS)). Cost-effectiveness is not an argument for restricting testing to younger patients or those with a strong family history. Universal testing for Lynch syndrome in endometrial cancer patients is expected to be cost-effective in the U.K. (NHS), and the Manchester approach is expected to be the optimal testing strategy.


Author(s):  
Sawsan Ibrahim AlMukdad ◽  
Hazem Elewa ◽  
Daoud Al-Badriyeh

Background: Patients having CYP2C19 loss-of-function alleles and receiving clopidogrel are at higher risk of adverse cardiovascular outcomes. Ticagrelor is a more effective and expensive antiplatelet that is unaffected by the CYP2C19 polymorphism. The main aim of the current research is to evaluate the cost-effectiveness among CYP2C19 genotype-guided therapy, universal ticagrelor, and universal clopidogrel after a percutaneous coronary intervention (PCI). Methods: A two-part simulation model, including a one-year decision-analytic model and a 20-year followup Markov model, was created to follow the use of (i) universal clopidogrel, (ii) universal ticagrelor, and (iii) genotype-guided antiplatelet therapy. Outcome measures were the incremental cost-effectiveness ratio (ICER, cost/success) and incremental cost-utility ratio (ICUR, cost/qualityadjusted life years [QALY]). Therapy success was defined as survival without myocardial infarction, stroke, cardiovascular death, stent thrombosis, and no therapy discontinuation because of adverse events, i.e. major bleeding and dyspnea. The model was based on a multivariate analysis, and a sensitivity analysis confirmed the robustness of the model outcomes. Results: Against universal clopidogrel, genotype-guided therapy was cost-effective over the one-year duration (ICER, USD 6,102 /success), and dominant over the long-term. Genotype-guided therapy was dominant over universal ticagrelor over the one-year duration and cost-effective over the long term (ICUR, USD 1,383 /QALY). Universal clopidogrel was dominant over ticagrelor over the short term, and cost-effective over the long-term (ICUR, 10,616 /QALY). Conclusion: CYP2C19 genotype-guided therapy appears to be the preferred antiplatelet strategy, followed by universal clopidogrel, and then universal ticagrelor for post-PCI patients in Qatar.


PLoS ONE ◽  
2021 ◽  
Vol 16 (11) ◽  
pp. e0258605
Author(s):  
Qiao Liu ◽  
Chongqing Tan ◽  
Lidan Yi ◽  
Xiaomin Wan ◽  
Liubao Peng ◽  
...  

Background The phase III KEYNOTE-604 study confirmed the benefit of pembrolizumab combined with chemotherapy in the first-line treatment of extensive-stage small-cell lung cancer (ES-SCLC). Taken into account the clinical benefits of pembrolizumab and its high cost, this study aimed to assess the cost-effectiveness of adding pembrolizumab to standard first-line etoposide-platinum (EP) for patients with ES-SCLC from the US payer perspective. Methods A Markov model was developed to compare the cost and quality-adjusted life-year (QALY) of pembrolizumab plus EP and placebo plus EP over a 10-year time horizon. Clinical efficacy and safety data were pooled from the KEYNOTE-604 trial. Utilities were obtained from published resources. Costs were mainly collected from Medicare in 2020. Sensitivity analyses were performed to examine the robustness of our model. Results Adding pembrolizumab to standard first-line EP resulted in the better effectiveness than EP chemotherapy alone for ES-SCLC by 0.22 QALYs. Pembrolizumab plus EP was dominated economically by placebo plus EP, leading to an incremental cost-effectiveness ratio (ICER) of $334,373/ QALY. Deterministic sensitivity analyses indicated that the uncertainty in model parameters exerted no substantial effect on our results. Probability sensitivity analysis indicated that probabilities for pembrolizumab plus EP being cost-effective within a wide range of willingness to pay were modest. Conclusion From the US payer perspective, the first-line treatment for ES-SCLC with pembrolizumab plus EP was not cost-effective compared with placebo plus EP. Although pembrolizumab combination chemotherapy was beneficial to the survival of ES-SCLC, price reduction may be the necessary to improve its cost-effectiveness.


2021 ◽  
Vol 19 (1) ◽  
Author(s):  
E. M. Saldarriaga ◽  
J. Bravo-Zúñiga ◽  
Y. Hurtado-Roca ◽  
V. Suarez

Abstract Background The Renal Health Program (RHP) was implemented in 2013 as a secondary prevention strategy to reduce the incidence of patients initiating dialysis and overall mortality. A previous study found that adherent patients have 58% protection against progression to dialysis compared to non-adherent. The main objective of the study was to estimate the lifetime economic and health consequences of the RHP intervention to determine its cost-effectiveness in comparison with usual care. Methods We use a Markov model of three health stages to simulate disease progression among chronic kidney disease patients in Lima, Peru. The simulation time-horizon was 30 years to capture the lifetime cost and health consequences comparing the RHP to usual care. Costs were estimated from the payer perspective using institutional data. Health outcomes included years lived free of dialysis (YL) and quality adjusted life years (QALY). We conducted a probabilistic sensitivity analysis (PSA) to assess the robustness of our estimates against parameter uncertainty. Results We found that the RHP was dominant—cost-saving and more effective—compared to usual care. The RHP was 783USD cheaper than the standard of care and created 0.04 additional QALYs, per person. The Incremental Cost-Effectiveness Ratio (ICER) showed a cost per QALY gained of $21,660USD. In the PSA the RHP was dominant in 996 out of 1000 evaluated scenarios. Conclusions The RHP was cheaper than the standard of care and more effective due to a reduction in the incidence of patients progressing to dialysis, which is a very expensive treatment and many times inaccessible. We aim these results to help in the decision-making process of scaling-up and investment of similar strategies in Peru. Our results help to increase the evidence in Latin America where there is a lack of information in the long-term consequences of clinical-management-based prevention strategies for CKD patients.


2021 ◽  
Vol 11 ◽  
Author(s):  
SiNi Li ◽  
JianHe Li ◽  
LiuBao Peng ◽  
YaMin Li ◽  
XiaoMin Wan

IntroductionRecently, a phase III CROWN trial compared the efficacy of two anaplastic lymphoma kinase (ALK) inhibitors and demonstrated that lorlatinib displayed clinical improvement over crizotinib for advanced non-small cell lung cancer (NSCLC) patients. Therefore, the aim of this study was to estimate the cost-effectiveness of lorlatinib as a first-line therapy for patients with advanced ALK-positive (+) NSCLC.Materials and MethodsA cost-effectiveness analysis was performed using a microsimulation model from the US payer perspective and a lifetime horizon (30 years) in patients with previous untreated advanced ALK+ NSCLC. Based on the CROWN trial, patient characteristics were obtained, and the transition probabilities were estimated. All direct costs were derived from official sources and published literature. The main outcomes of the model were total costs, incremental cost-effectiveness ratio (ICER), quality-adjusted life years (QALYs), and life years (LYs). One-way and probabilistic sensitivity analyses and multiple scenario analyses were conducted to test the robustness of the model outcomes.ResultsIn the base case analysis, in which 1 million patients were simulated, treatment with lorlatinib or crizotinib as the first-line treatment was related to a mean cost of $909,758 and $616,230 (incremental cost: $293,528) and a mean survival of 4.81 QALYs and 4.09 QALYs (incremental QALY: 0.72) per patient, respectively. The main drivers of cost effectiveness were drug price and subsequent cost. PAS indicated that lorlatinib has 90% cost-effectiveness when compared to crizotinib when the willingness-to-pay (WTP) threshold in increased to $448,000/QALY. Scenario analysis demonstrated that lorlatinib has 100% cost-effectiveness at a WTP threshold of 200,000/QALY compared to crizotinib treatment when the price of lorlatinib is decreased to 75% ($424.5) of its original price.ConclusionsIn this study, lorlatinib was unlikely to be cost effective compared with crizotinib for patients with previously untreated advanced ALK+ NSCLC at a WTP threshold of 200,000/QALY.


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