Cost-effectiveness of consolidation durvalumab for inoperable stage III non-small cell lung cancer in Vietnam.

BACKGROUND: This study aimed to assess the cost-effectiveness of durvalumab as a treatment option for patients with inoperable stage III non-small cell lung cancer (NSCLC) from healthcare and partial societal perspectives in Vietnam. METHOD: A lifetime partitioned survival model was used to evaluate the costs and quality-adjusted life years (QALYs) associated with consolidation durvalumab in comparison with the standard of care alone. Local costs and utilities were incorporated into the model. In the base-case analysis, no discount was applied to the acquisition cost of durvalumab. Scenario-based, one-way and probabilistic-sensitivity analyses were conducted. RESULTS: The base-case analysis revealed that the intervention resulted in an increase of 1.38 life years or 1.08 QALYs for patients, but the intervention was not deemed cost-effective from either perspective in the base-case analysis. However, with a 70% reduction in the durvalumab acquisition cost, the intervention was observed to be cost-effective when evaluated from a healthcare perspective and when examining the undiscounted results from a partial societal standpoint. CONCLUSION: This study provides evidence regarding the cost-effectiveness of durvalumab for the treatment of inoperable stage III NSCLC in Vietnam for various scenarios. The intervention was not cost-effective at full acquisition cost, but it is important to acknowledge that cost-effectiveness arguments alone cannot solely guide decision-makers in Vietnam; other criteria, such as budget impact and ethical concerns, are crucial factors to consider in decision-making processes.

Health and Economic Outcomes of Pembrolizumab in the Treatment of Metastatic Non-small Cell Lung Cancer (mNSCLC) and Melanoma in Italy.

BACKGROUND AND OBJECTIVE: In Italy, the management of metastatic non-small cell lung cancer and melanoma leads to significant healthcare challenges, necessitating cost-effective treatment strategies and offering valuable insights for healthcare policymakers and stakeholders. This study was designed to assess the costs, quality-adjusted life-years (QALYs) and disability-adjusted life-years (DALYs) associated with the health and economic outcomes of (1) pembrolizumab-combined chemotherapy administered as a first-line treatment for metastatic non-squamous and squamous non-small cell lung cancer (NSCLC) where the tumour presents with a programmed death-ligand 1 expression level < 50% and of (2) adjuvant pembrolizumab treatment for stage III melanoma. METHODS: Three cost-effectiveness models developed by MSD were investigated for each treatment indication. A unique model was built to assess the overall effect of pembrolizumab versus chemotherapy or watchful waiting in patients with lung cancer or melanoma, respectively. Theoretical cohorts of patients with metastatic squamous and non-squamous NSCLC were followed over time using a partitioned survival model with weekly cycles. A weekly cycle Markov model was employed for melanoma. The analysis was conducted from the Italian National Health Service perspective, considering a time horizon of 40 years (lifetime). A single closed cohort of treatable patients was followed over time for each indication (4000, 7000 and 900 for NSCLC squamous, non-squamous and melanoma, respectively). The costs evaluated included those for adverse drug events, non-drug disease management, subsequent treatment and terminal care. Drug acquisition and administration costs were excluded. RESULTS: For each treatment indication assessed, pembrolizumab produced downstream direct cost offsets (- €122,498,568, - €133,369,076 and - €32,993,242 for NSCLC squamous, non-squamous and melanoma indications, respectively), increased quality of life (+2088, +5317 and +2307 QALYs for NSCLC squamous, non-squamous and melanoma indications, respectively) and reduced disability (- 2658, - 7202 and - 3029 DALYs for NSCLC squamous, non-squamous and melanoma indications, respectively). Across indications, the total cost offsets of pembrolizumab were - €288,860,885, with 9712 QALYs gained and 12,889 DALYs avoided. CONCLUSIONS: The analysis demonstrated that, compared with chemotherapy, pembrolizumab is more cost effective in Italy as a first-line treatment in patients with metastatic squamous or non-squamous NSCLC and, if compared with watchful waiting, as adjuvant treatment in patients with stage III melanoma. The present analysis suggested that pembrolizumab use could lead to important health benefits for patients while offsetting a portion of cancer care costs.

Budget impact analysis of the novel PD-1 inhibitor toripalimab versus pembrolizumab in recurrent or metastatic nasopharyngeal carcinoma.

AIM: To estimate the budget impact of adding a toripalimab regimen as a treatment option to the existing pembrolizumab regimen, both including gemcitabine and cisplatin, in untreated recurrent/metastatic nasopharyngeal carcinoma (R/M NPC) using the published wholesale acquisition cost (WAC) and average sales price (ASP). METHODS: Budget impact analysis comparing a treatment mix "without" versus "with" the toripalimab regimen in the US eligible annual incident R/M NPC population, a 3-year time horizon, toripalimab/pembrolizumab market splits of 60/40 (Y1) and 80/20 (Y2/3), and medication adjustments for discontinuation or progression. Cost inputs included drugs, administration, and adverse event (AE) management. The models were replicated for a hypothetical 1-million-member health plan in which costs per-member-per-month (PMPM) and per-member-per-year (PMPY) were estimated. One-way (OWSA) and probabilistic sensitivity analyses (PSA) as well as scenario analyses were performed. RESULTS: In the "without" scenario, the 3-year WAC-based costs for the pembrolizumab regimen total $1,449,695,333 ($1,305,632,448 for treatment and $144,062,885 for managing AEs). In the "with" scenario, total 3-year costs for pembrolizumab decline to $380,012,135 with toripalimab adding $885,505,900 ($779,206,567 for treatment and $106,299,333 for AE management). Annual net savings range from $46,526,152 in 2024 to $71,194,214 in 2026, for 3-year savings of $184,177,298. Associated net savings in a 1-million-member health plan are $543,068 over 3 years with savings of $0.045 PMPM and $0.543 PMPY. The ASP-based model shows similar patterns with 3-year net savings of $174,235,983 in the US incident population and savings of $0.043 PMPM and $0.514 PMPY in a 1-million-member health plan. The PSA support base case findings; OWSA and scenario analyses reveal how parameter variability impacts results. CONCLUSION: Savings between $174 million and $184 million can be achieved from treating 60% of R/M NPC patients in year 1 and 80% in years 2 and 3 with the toripalimab regimen over a similar pembrolizumab regimen.

Toripalimab, a human monoclonal anti-body that targets PD-1, was recently approved by the US Food and Drug Administration (FDA) for the first-line treatment of adults with metastatic or recurrent, locally advanced nasopharyngeal carcinoma (NPC), in combination with gemcitabine and cisplatin. We evaluated how much it would cost a payor to cover the FDA-approved toripalimab plus gemcitabine and cisplatin regimen (the toripalimab regimen) to a non-FDA-approved pembrolizumab plus gemcitabine and cisplatin regimen (the pembrolizumab regimen). With no trial data available for such pembrolizumab regimen, we assumed that it would be comparable to the toripalimab regimen in efficacy and safety. Our model adopted a 3-year time horizon and assumed a 60/40 market share split in year 1 and an 80/20 market split in years 2 and 3. It included two US cost inputs: the wholesale acquisition cost (WAC) or "list price" at market entry and, as no average sales price (ASP) will be available for toripalimab for several quarters, a toripalimab price point of 80% of the pembrolizumab ASP. We adjusted for patients whose cancer progressed or who discontinued treatment to determine the number of fully-treated-patient-equivalents. We found that treating 60% of NPC patients in year 1 and 80% in years 2 and 3 with the toripalimab regimen instead of the pembrolizumab regimen generates, for the entire adjusted patient population, savings ranging from $174 million when using ASP to $184 million when using WAC.

Cost-effectiveness analysis of bevacizumab for cerebral radiation necrosis treatment based on real-world utility value in China.

BACKGROUND: Bevacizumab shows superior efficacy in cerebral radiation necrosis (CRN) therapy, but its economic burden remains heavy due to the high drug price. This study aims to evaluate the cost-effectiveness of bevacizumab for CRN treatment from the Chinese payers' perspective. METHODS: A decision tree model was developed to compare the costs and health outcomes of bevacizumab and corticosteroids for CRN therapy. Efficacy and safety data were derived from the NCT01621880 trial, which compared the effectiveness and safety of bevacizumab monotherapy with corticosteroids for CRN in nasopharyngeal cancer patients, and demonstrated that bevacizumab invoked a significantly higher response than corticosteroids (65.5% vs. 31.5%, P < 0.001) with no significant differences in adverse events between two groups. The utility value of the "non-recurrence" status was derived from real-world data. Costs and other utility values were collected from an authoritative Chinese network database and published literature. The primary outcomes were total costs, quality-adjusted life-years (QALYs), and incremental cost-effectiveness ratio (ICER). The uncertainty of the model was evaluated via one-way and probabilistic sensitivity analyses. RESULTS: Bevacizumab treatment added 0.12 (0.48 vs. 0.36) QALYs compared to corticosteroid therapy, along with incremental costs of $ 2010 ($ 4260 vs. $ 2160). The resultant ICER was $ 16,866/QALY, which was lower than the willingness-to-pay threshold of $ 38,223/QALY in China. The price of bevacizumab, body weight, and the utility value of recurrence status were the key influential parameters for ICER. Probabilistic sensitivity analysis revealed that the probability of bevacizumab being cost-effectiveness was 84.9%. CONCLUSION: Compared with corticosteroids, bevacizumab is an economical option for CRN treatment in China.

Cost-effectiveness of treating relapsed or refractory 3L+ follicular lymphoma with axicabtagene ciloleucel vs mosunetuzumab in the United States.

Introduction: Novel therapies for 3L+ relapsed/refractory (r/r) follicular lymphoma (FL) have been approved recently by the US Food and Drug Administration including anti-CD19 CAR-T therapies such as axicabtagene ciloleucel (axi-cel) and CD20 × CD3 T-cell-engaging bispecific monoclonal antibodies such as mosunetuzumab (mosun). The objective of this study was to assess the cost-effectiveness of axi-cel compared to mosun in 3L+ r/r FL patients from a US third-party payer perspective. Methods: A three-state (progression-free, progressed disease, and death) partitioned-survival model was used to compare two treatments over a lifetime horizon in a hypothetical cohort of US adults (age ≥18) receiving 3L+ treatment for r/r FL. ZUMA-5 and GO29781 trial data were used to inform progression-free survival (PFS) and overall survival (OS). Mosun survival was modeled via hazard ratios (HRs) applied to axi-cel survival curves. The PFS HR value was estimated via a matching-adjusted indirect comparison (MAIC) based on mosun pseudo-individual patient data and adjusted axi-cel data to account for trial populations differences. One-way sensitivity analysis (OWSA) and probabilistic sensitivity analyses (PSA) were conducted. Scenario analyses included: 1) the mosun HRs were applied to the weighted (adjusted) ZUMA-5 24-month data to most exactly reflect the MAIC, 2) mosun HR values were applied to axi-cel 48-month follow-up data, and 3) recent axi-cel health state utility values in diffuse large B-cell lymphoma patients. Results: The analysis estimated increases of 1.82 LY and 1.89 QALY for axi-cel compared to mosun. PFS for axi-cel patients was 6.42 LY vs. 1.60 LY for mosun. Increase of $257,113 in the progression-free state was driven by one-time axi-cel treatment costs. Total incremental costs for axi-cel were $204,377, resulting in an ICER of $108,307/QALY gained. The OWSA led to ICERs ranging from $240,255 to $75,624, with all but two parameters falling below $150,000/QALY. In the PSA, axi-cel had an 64% probability of being cost-effective across 5,000 iterations using a $150,000 willingness-to-pay threshold. Scenarios one and two resulted in ICERs of $105,353 and $102,695, respectively. Discussion: This study finds that axi-cel is cost-effective compared to mosun at the commonly cited $150,000/QALY US willingness-to-pay threshold, with robust results across a range of sensitivity analyses accounting for parameter uncertainty.

Quality-adjusted life years for HER2-positive, early-stage breast cancer using trastuzumab-containing regimens in the context of cost-effectiveness studies: a systematic review.

INTRODUCTION: This study aims to provide a comprehensive assessment of economic and health-related quality of life (HRQoL) outcomes for human epidermal growth factor receptor 2 (HER2)-positive, early-stage breast cancer patients treated with trastuzumab-containing regimens, by focusing on both Incremental Cost-Effectiveness Ratios (ICERs) and quality-adjusted life years (QALYs). METHODS: A systematic search was conducted across PubMed, Embase, and Scopus databases without language or publication year restrictions. Two independent reviewers screened eligible studies, extracted data, and assessed methodology and reporting quality using the Drummond checklist and Consolidated Health Economic Evaluation Reporting Standards 2022 (CHEERS 2022), respectively. Costs were converted to US dollars (US$) for 2023 for cross-study comparison. RESULTS: Twenty-two articles, primarily from high-income countries (HICs), were included, with ICERs ranging from US$13,176/QALY to US$254,510/QALY, falling within country-specific cost-effectiveness thresholds. A notable association was observed between higher QALYs and lower ICERs, indicating a favorable cost-effectiveness and health outcome relationship. EQ-5D was the most utilized instrument for assessing health state utility values, with diverse targeted populations. CONCLUSIONS: Studies reporting higher QALYs tend to have lower ICERs, indicating a positive relationship between cost-effectiveness and health outcomes. However, challenges such as methodological heterogeneity and transparency in utility valuation persist, underscoring the need for standardized guidelines and collaborative efforts among stakeholders. REGISTRATION: PROSPERO ID: CRD42021259826.

International Cost-Effectiveness Analysis of Durvalumab in Stage III Non-Small Cell Lung Cancer.

Importance: Standard of care for unresectable locally advanced non-small cell lung cancer (NSCLC) involves definitive chemoradiotherapy followed by maintenance therapy with durvalumab. However, the cost of durvalumab has been cited as a barrier to its use in various health systems. Objective: To evaluate the cost-effectiveness of durvalumab vs placebo as maintenance therapy in patients with unresectable stage III NSCLC from 4 international payer perspectives (US, Brazil, Singapore, and Spain). Design, Setting, and Participants: In this economic evaluation, a Markov model was designed to compare the lifetime cost-effectiveness of maintenance durvalumab for unresectable stage III NSCLC with that of placebo, using 5-year outcomes data from the PACIFIC randomized placebo-controlled trial. Individual patient data were extracted from the PACIFIC, KEYNOTE-189, ADAURA, ALEX, and REVEL randomized clinical trials to develop a decision-analytic model to determine the cost-effectiveness of durvalumab compared with placebo maintenance therapy over a 10-year time horizon. Direct costs, adverse events, and patient characteristics were based on country-specific payer perspectives and demographic characteristics. The study was conducted from June 1, 2022, through December 27, 2023. Main Outcomes and Measures: Life-years, quality-adjusted life years (QALYs), lifetime costs, and incremental cost-effectiveness ratios (ICERs) were estimated at country-specific willingness-to-pay thresholds ([data reported in US$] US: $150 000 per QALY; Brazil: $22 251 per QALY; Singapore: $55 288 per QALY, and Spain: $107 069 per QALY). One-way and probabilistic sensitivity analyses were performed to account for parameters of uncertainty. A cost-threshold analysis was also performed. Results: The US base-case model found that treatment with durvalumab was associated with an increased cost of $114 394 and improved effectiveness of 0.50 QALYs compared with placebo, leading to an ICER of $228 788 per QALY. Incremental cost-effectiveness ratios, according to base-case models, were $141 146 for Brazil, $153 461 for Singapore, and $125 193 for Spain. Durvalumab price adjustments to the PACIFIC data improved cost-effectiveness in Singapore, with an ICER of $45 164. The model was most sensitive to the utility of durvalumab. Conclusions and Relevance: In this cost-effectiveness analysis of durvalumab as maintenance therapy for unresectable stage III NSCLC, the therapy was found to be cost-prohibitive from the perspective of various international payers according to country-specific willingness-to-pay thresholds per QALY. The findings of the study suggest that discounted durvalumab acquisition costs, as possible in Singapore, might improve cost-effectiveness globally.

Economic evaluation of trastuzumab in HER2-positive early breast cancer in Indonesia: A cost-effectiveness analysis.

BACKGROUND: Trastuzumab has significantly enhanced the survival and prognosis of individuals diagnosed with human epidermal growth factor receptor 2 (HER2)-positive early breast cancer. Considering its relatively high costs, we aimed to examine the cost-effectiveness of trastuzumab plus chemotherapy compared with chemotherapy alone in HER2-positive early breast cancer from an Indonesian healthcare payer's perspective. METHODS: A Markov model was developed to project the lifetime health benefits and costs associated with trastuzumab treatment for a cohort of women with HER2-positive early breast cancer. Efficacy data and baseline characteristics in the base-case analysis were primarily derived from the 11-year results of the HERA trial. Costs were based on verified reimbursement data from Indonesia's Health and Social Security Agency (BPJS Kesehatan) of the year 2020. A scenario analysis was conducted with efficacy data based on the joint analysis from the NSABP B-31 and NCCTG N9831 trials, allowing for subgroup analysis by age at diagnosis. Univariate and probabilistic sensitivity analyses were conducted to assess the influence of parameter uncertainty. RESULTS: In the base-case analysis, the results indicated that the lifetime costs for trastuzumab plus chemotherapy and chemotherapy alone were US$33,744 and US$22,720, respectively, resulting in substantial incremental savings of US$11,024 per patient for the former. Trastuzumab plus chemotherapy also led to higher total quality-adjusted life years (QALYs) and life years gained (LYG), resulting in incremental cost-effectiveness ratios (ICERs) of US$6,842 per QALY and US$5,510 per LYG. In scenario analysis, the subgroup with an age at diagnosis <40 years old reflected the most cost-effective subgroup. Both the base-case and scenario analyses demonstrated cost-effectiveness with a willingness-to-pay threshold of three-times Gross Domestic Product (GDP). Sensitivity analyses confirmed the robustness of the findings and conclusions. CONCLUSION: In Indonesia, trastuzumab plus chemotherapy can be considered cost-effective compared to chemotherapy alone at a willingness-to-pay threshold of three times GDP, and it is likely most cost-effective in women <40 years of age.

Real-world data on efficacy/safety and economic impact of nivolumab administered every 2 and 4 weeks among Japanese patients.

AIM: A new treatment interval for nivolumab administration at 480 mg every 4 weeks, in addition to 240 mg every 2 weeks, was approved in Japan in 2020. Using model-based evaluation, it was speculated that the effects or safety of nivolumab do not differ between the two treatment intervals; however, real-world data on nivolumab efficacy, safety, and economic impact are lacking. Accordingly, we aimed to examine the effects of nivolumab treatment intervals (2 weeks vs. 4 weeks) in terms of efficacy, safety, and economic impact in Japanese patients with cancer. METHODS: We retrospectively analyzed 126 patients treated with nivolumab. The patients were divided into two groups depending on whether they received nivolumab at 240 mg every 2 weeks (2-week group) or 480 mg every 4 weeks (4-week group). RESULTS: Efficacy results found no significant difference between the 4- and 2-week groups considering median overall survival (p = 0.70) and median progression-free survival (p = 0.57). The incidence of any grade and ≥  grade 3 immune-related adverse events did not differ between the 4-week and 2-week groups (any grade, p = 0.13; ≥  grade 3, p = 0.36). Excluding drug costs, the 4-week group had significantly lower medical costs than the 2-week group (2-week vs. 4-week: mean, 94,659 JPY [679.0 USD] vs. 58,737 JPY [421.3 USD]; p < 0.05). CONCLUSION: Collectively, our findings suggest that nivolumab 480 mg every 4 weeks may be more effective than nivolumab 240 mg every 2 weeks in terms of economic impact.

Tackling Challenges in Assessing the Economic Value of Tumor-Agnostic Therapies: A Cost-Effectiveness Analysis of Pembrolizumab as a Case Study.

OBJECTIVES: Assessing the value of tumor-agnostic drugs (TAD) is challenging given the potential variability in treatment effects, trials with small sample sizes, different standards of care (SoC), and lack of comparative data from single-arm basket trials. Our study developed and applied novel methods to assess the value of pembrolizumab compared with SoC to inform coverage decisions. METHODS: We developed a partitioned survival model to evaluate the cost-utility of pembrolizumab for previously treated patients with 8 advanced or metastatic microsatellite instability-high or mismatch repair-deficient cancers from a US commercial payer perspective. Efficacy of pembrolizumab was based on data from trials directly or with adjustment using Bayesian hierarchical models. Eight chemotherapy-based external control arms were constructed from the TriNetX electronic health record databases. Tumor-specific health-state utility values were applied. All costs were adjusted to 2022 US dollars. RESULTS: At a lifetime horizon, pembrolizumab was associated with increased effectiveness compared with chemotherapies in colorectal (quality-adjusted life years [QALYs]: +0.64, life years [LYs]: +0.64), endometrial (QALYs: +3.79, LYs: +5.47), and small intestine cancers (QALYs: +1.73, LYs: +2.48), but not for patients with metastatic gastric, cholangiocarcinoma, pancreatic, ovarian, and brain cancers. Incremental cost-effectiveness ratios varied substantially across tumor types. Pembrolizumab was found to be cost-effective in treating colorectal and endometrial cancers (incremental cost-effectiveness ratios: $121 967 and $139 257, respectively), and not cost-effective for other assessed cancers at a $150 000 willingness-to-pay/QALY threshold, compared with SoC chemotherapies. CONCLUSIONS: The cost-effectiveness of TADs can vary by cancers. Using analytic tools such as external controls and Bayesian hierarchical models can tackle several challenges in assessing the value of TADs and uncertainties from basket trials.

Cost-effectiveness of tisotumab vedotin as a second- or third-line therapy for cervical cancer.

OBJECTIVE: To evaluate the cost-effectiveness of tisotumab vedotin to treat recurrent or metastatic cervical cancer in second- or third-line from the U.S. payer perspective. METHODS: A Markov model with three-state was employed to simulate recurrent or metastatic cervical cancer patients who were administered either tisotumab vedotin or investigator's choice of chemotherapy based on the phase III, open-labeled innovaTV 301 randomized clinical trial. The data on cost and health preferences were collected from the literature. RESULTS: Tisotumab vedotin generated an additional 0.25 quality-adjusted life-years (QALYs) compared to chemotherapy, but at an additional cost of $206,779. This results in incremental cost-effectiveness ratios of $839,107.88 per QALY. The results of the univariate sensitivity analysis indicated that cost of tisotumab vedotin, utility of progressive disease and progression-free survival had the greatest impacts on the outcomes. Probability sensitivity analysis showed that tisotumab vedotin had a 0% chance of being considered cost-effective. CONCLUSION: Tisotumab vedotin was unlikely cost-effective compared to chemotherapy for recurrent or metastatic cervical cancer patients at a willingness-to-pay threshold of $150,000/QALY from the perspective of a U.S. payer. Lowering the prices of tisotumab vedotin could potentially enhance its cost-effectiveness.

Cost-effectiveness analysis of PD-1 inhibitors as second-line therapy for advanced or metastatic esophageal squamous cell carcinoma in China: an economic evaluation based on network meta-analysis.

BACKGROUND: Several economic studies have assessed the cost-effectiveness of programmed cell death protein-1 (PD-1) inhibitors compared to second-line chemotherapy in treating esophageal squamous cell carcinoma (ESCC). However, there is a lack of economic comparisons among the different PD-1 inhibitors. AIM: This study aimed to assess the cost-effectiveness of PD-1 inhibitors (nivolumab, pembrolizumab, camrelizumab, and tislelizumab) in second-line treatment for advanced or metastatic ESCC within the Chinese healthcare system. METHOD: The clinical trials were systematically retrieved from PubMed, Embase, Web of Science, and the Cochrane Library. We established a fractional polynomials model to conduct a network meta-analysis, enabling the calculation of hazard ratios and expected survival rates. Economic outcomes were estimated using a partitioned survival model. The costs and utilities were gathered from published sources. The threshold for willingness-to-pay (WTP) for a quality-adjusted life year (QALY) was set at three times China's per capita gross domestic product in 2022. Sensitivity analyses (SA) were performed to address uncertainties in the model. RESULTS: Four phase III randomized controlled trials were included, evaluating the cost-effectiveness of four PD-1 inhibitors, camrelizumab, nivolumab, tislelizumab, and pembrolizumab, compared to chemotherapy for the second-line treatment of advanced or metastatic ESCC. For camrelizumab, nivolumab, tislelizumab, and pembrolizumab, the corresponding incremental cost-effectiveness ratios were $27,375.43/QALY, $205,312.19/QALY, $9,266.73/QALY, and $220,368.10/QALY, respectively. The SA results indicated the robustness of the base analysis findings. CONCLUSION: From the Chinese healthcare system, under the WTP of $38,253.48/QALY, tislelizumab is a cost-effective treatment option for the second-line treatment of advanced or metastatic ESCC.

The impact of an 'evergreening' strategy nearing patent expiration on the uptake of biosimilars and public healthcare costs: a case study on the introduction of a second administration form of trastuzumab in The Netherlands.

In this paper, we explore dynamic market share and public healthcare costs of trastuzumab's evergreening (subcutaneous) variant during introduction of trastuzumab's competitive biosimilar variants in the Netherlands. We used a time series design to assess dynamic market share of trastuzumab's evergreening variant after introducing trastuzumab's biosimilar variants, focusing on the number of treatments and patients. The public healthcare costs of this evergreening strategy were estimated using administrative claims data. Our results show that the original trastuzumab was completely replaced by the subcutaneous and biosimilar variants. The uptake of the subcutaneous form peaked at 50% market share but after the introduction of biosimilars progressively reduced to a market share of 20%, resulting in a more competitive market structure. The public healthcare costs for trastuzumab significantly decreased after the introduction of the biosimilars. After the introduction of the biosimilars, a substantial price drop is visible, with the subcutaneous version, still under patent, also falling sharply in price but less strongly than the iv/biosimilar version. As the costs are publicly funded, we recommend a more explicit societal debate to consider if the potential benefits of subcutaneous Herceptin® (and other similar medicines) are worth the additional costs, and at which price it should be reimbursed as the part of the benefit package.

Budget Impact Analysis of Idecabtagene Vicleucel for the Treatment of Adult Patients with Relapsed or Refractory Multiple Myeloma in the US.

BACKGROUND: Gene therapy is known to be unaffordable to those who need it the most; however, evidence on the financial impact is limited. OBJECTIVE: This study aimed to estimate the budget impact and affordability of the gene therapy idecabtagene vicleucel for the treatment of adult patients with relapsed or refractory multiple myeloma (rrMM) in the US over a 3-year period from the payer healthcare perspective. METHOD: A budget impact model was developed to estimate the budget impact to the US healthcare plan compared with bortezomib-based maintenance therapy. The target population size was based on a hypothetical 1-million-member plan over a 3-year time horizon with and without idecabtagene vicleucel adoption. The cost of drug acquisition, drug administration, and grade 3-4 adverse events (AEs) were calculated for both scenarios. The budget impact of idecabtagene vicleucel was calculated as the difference in costs for these two scenarios. Costs were extracted from IBM-Micromedex Red Book, Centers for Medicare and Medicaid Services, and the literature. A one-way sensitivity analysis was performed to ensure robustness. RESULTS: An estimated 22 patients with rrMM each year would be eligible for idecabtagene vicleucel. The model projected the annual cost per patient in the first year as $19,449 and $517,528.13 for bortezomib and idecabtagene vicleucel, respectively. Introducing idecabtagene vicleucel was predicted to increase the total budget by $13.4, $13.6, and $14 million in the first, second, and third years. There would be an additional $1.1128, $1.1252, and $1.1486 per member per month (PMPM) when using idecabtagene vicleucel over bortezomib. CONCLUSION: This study suggests that the high cost of the gene therapy idecabtagene vicleucel is justifiable due to the low number of rrMM patients.

Cost-effectiveness of nivolumab plus ipilimumab as first-line treatment for American patients with unresectable malignant pleural mesothelioma.

Background: The treatment paradigm of unresectable malignant pleural mesothelioma (MPM) has changed in recent years. Checkmate 743 demonstrate that nivolumab plus ipilimumab showed good clinical benefits compared with chemotherapy in the treatment of MPM. The study is aim to evaluate the cost-effectiveness of Nivolumab plus ipilimumab vs. platinum plus chemotherapy for the first-line treatment of unresectable MPM. Methods: A Markov model was developed to compare the cost and quality-adjusted life-year (QALY) of nivolumab plus ipilimumab and chemotherapy over a 10-year time horizon. Clinical efficacy and safety data were extracted from the CheckMate 743 trials. Health state utilities were obtained from published literature. Costs were collected from an US payer perspective. One-way and probabilistic sensitivity analyses were conducted to explore the impact of uncertainties on the cost-effectiveness's results. Results: In the base case analysis, the incremental healthcare costs and QALYs for Nivolumab plus Ipilimumab vs. chemotherapy are $196,604.22 and 0.53, respectively, resulting an incremental cost-effectiveness ratio (ICER) of $372,414.28/QALYs for the model cohort of patients with locally advanced or metastatic MPM. However, Probabilistic sensitivity analysis showed that there was no probability that Nivolumab plus ipilimumab was cost-effective within the fluctuation range of other model parameters in first-line in unresectable MPM. The results of one-way sensitivity analysis showed that the cost of Nivolumab was the most sensitive parameter. Conclusions: The ICER of Nivolumab plus ipilimumab is above the theoretical willingness-to-pay threshold in the U.S, which suggests that first-line nivolumab plus ipilimumab for unresectable MPM may be not a cost-effective choice.

[Administrative delays of temporary recommendation for use: Impact on access to innovation in melanoma]. / Délais administratifs des RTU, effet sur l'accès à l'innovation dans le mélanome.

INTRODUCTION: Melanoma has benefited in recent years from therapeutic innovations, which have improved overall survival of patients. France has developed a regulatory arsenal allowing faster access to innovative drugs before marketing authorization: temporary authorization for use (ATU) and temporary recommendation for use (RTU). METHOD: We describe here the decision-making processes that led to the non-publication of the decree on the funding of three RTU in adjuvant melanoma therapy: nivolumab, pembrolizumab and the combination of dabrafenib and trametinib, and we analyse the fate of these drugs in order to quantify the potential loss of chance. RESULTS: On 03AUG2018, the French National Agency for Medicines and Health Product Safety (ANSM) published 3 RTU in order to give rapid access to major innovations in adjuvant melanoma therapy: nivolumab, pembrolizumab and the combination of dabrafenib and trametinib. These drugs have respectively demonstrated reductions in the risk of recurrence by 35 %, 43% and 55% for target populations of 2200, 1900 and 650 patients per year. Despite a favourable opinion on reimbursement from the French National Authority for Health (HAS), the decrees on reimbursement will never be published, prohibiting the use of these products before the marketing authorisation, and depriving many patients of a potential cure. CONCLUSION: Despite a favourable opinion from scientists and health agencies for the rapid availability of a drug, the French public health code does not systematically imply access to a therapeutic innovation. The reform of access to innovation implemented on 01JUL2021 may help tackle this issue.

Cost-Effectiveness of Cemiplimab Versus Standard of Care in the United States for First-Line Treatment of Advanced Non-small Cell Lung Cancer With Programmed Death-Ligand 1 Expression ≥50.

OBJECTIVES: This study aimed to evaluate the cost-effectiveness, from a US commercial payer perspective, of cemiplimab versus other first-line treatments for advanced non-small cell lung cancer with programmed death-ligand 1 expression ≥50%. METHODS: A 30-year "partitioned survival" model was constructed. Overall survival and progression-free survival were estimated by applying time-varying hazard ratios from a network meta-analysis of randomized clinical trials. Overall survival and progression-free survival were estimated from EMPOWER-Lung 1 (cemiplimab monotherapy vs chemotherapy) and KEYNOTE-024 and KEYNOTE-042 (pembrolizumab monotherapy vs chemotherapy). Drug acquisition costs were based on published 2020 US list prices. A 3% discount rate was applied to life-years, quality-adjusted life-years (QALYs), and costs. A deterministic analysis was performed on the base case; 1-way sensitivity and probabilistic sensitivity analyses assessed model and parameter uncertainties. RESULTS: Cemiplimab was associated with increased time in the "preprogression" (13.08 vs 7.90 and 6.08 months) and "postprogression" (47.30 vs 29.49 and 14.78 months) health states versus pembrolizumab and chemotherapy, respectively. Compared with pembrolizumab and chemotherapy, cemiplimab generated 1.00 (95% CI -0.266 to 2.440) and 1.78 (95% CI 0.607-3.20) incremental QALYs, respectively, with incremental cost-effectiveness ratios of $68 254 and $89 219 per QALY for cemiplimab versus pembrolizumab and cemiplimab versus chemotherapy, respectively. The probability of cemiplimab being cost-effective at a willingness-to-pay threshold of $100 000 to $150 000 per QALY was 62% to 76% versus pembrolizumab and 56% to 84% versus chemotherapy. CONCLUSIONS: Findings suggest that cemiplimab, versus pembrolizumab or versus chemotherapy, is a cost-effective first-line treatment option for advanced non-small cell lung cancer with programmed death-ligand 1 expression ≥50%.