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.

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.

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.

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.

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.

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%.

[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 analysis of trastuzumab for early breast cancer in Brazil.

BACKGROUND: Adjuvant chemotherapy with trastuzumab for HER2 positive breast cancers has brought considerable benefits to disease-free survival and overall survival. OBJECTIVE: To conduct a cost-effectiveness analysis of the treatment of patients with early and locally advanced HER2 positive breast cancer, within the scope of the Brazilian public health system, comparing adjuvant chemotherapy with and without trastuzumab, for 1 year of treatment. METHODS: A 4-state Markov model was developed to estimate strategy costs and outcomes. RESULTS: Based on the proposed model, we verified an incremental benefit of trastuzumab therapy compared to treatment without trastuzumab with 0.84 quality-adjusted life years (QALY) and 1.16 life years gained (LYG). The use of adjuvant chemotherapy with trastuzumab has an ICER of US$19,599.26 for each quality-adjusted life year and US$14,180.68 for each life year gained in relation to chemotherapy without trastuzumab. CONCLUSION: In Brazil, adjuvant chemotherapy with trastuzumab may be considered cost-effective only if a cost-effectiveness threshold is stipulated with the value starting at three times the Brazilian GDP per capita for QALY or two times the Brazilian GDP per capita for LYG, from health system perspective.

Economic Evaluation of Monoclonal Antibodies in Metastatic Colorectal Cancer: A Systematic Review.

INTRODUCTION: Colorectal cancer (CRC) is one of the major causes of mortality and morbidity worldwide. The median overall survival (OS) of patients with metastatic CRC (mCRC) has doubled over the last 20 years partly due to the introduction of advanced biologic therapies. However, these treatment modalities bear significant costs on healthcare systems globally, and may jeopardize their fiscal sustainability. The aim of this systematic review was to critically appraise the economic evaluations of monoclonal antibodies in mCRC. METHODOLOGY: A literature search was performed in the electronic databases of: Cochrane Central Register of Controlled Trials, Cochrane Database of Systematic Reviews, Database of Abstracts of Reviews of Effects, EMBASE, EMBASE Alert, PUBMED, NHS Economic Evaluation and Health Technology Assessment Database for full articles published from 1 January 2013 to 31 December 2020. RESULTS: Twenty economic analyses were identified in the literature that fulfilled the inclusion criteria and evaluated the cost-effectiveness of (a) bevacizumab as first-line treatment for mCRC and as maintenance treatment, (b) cetuximab as first-line treatment, (c) panitumumab versus bevacizumab and cetuximab versus bevacizumab as first-line treatment, (d) aflibercept and ramucirumab as second-line treatment, (e) cetuximab and panitumumab as third-line treatment, (f) cetuximab versus panitumumab as later lines of treatment, and (g) RAS testing prior to anti-epidermal growth factor receptor (EGFR) treatment. CONCLUSIONS: Bevacizumab in combination with chemotherapy is cost-effective as neither first-line treatment nor maintenance treatment. Sequential treatment with bevacizumab in first-line and second-line treatment was also not cost-effective. Testing for KRAS and extended RAS mutations is cost-effective and should be performed prior to anti-EGFR treatment. In the RAS wild-type subgroup of mCRCs the use of anti-EGFR (panitumumab or cetuximab) in first-line treatment leads to a more favorable cost-effectiveness profile than the corresponding anti-VEGF (bevacizumab). Cetuximab is not cost-effective as a first-line treatment. Anti-EGFR administration is not a cost-effective strategy in third-line treatment, even for RAS wild-type mCRCs, compared to best supportive care. Aflibercept was superior to ramucirumab and costed less, but neither were cost-effective compared to standard care.

Cost-effectiveness analysis of pembrolizumab plus chemotherapy as first-line therapy for extensive-stage small-cell lung cancer.

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.

Challenges raised by the economic evaluation of CAR-T-cell therapies. The review by the French National Authority for Health.

Since 2013, the process of pricing of innovative drugs by the French National Health Insurance has considered both cost-effectiveness and budget impact. CAR-T cell therapies were first subject to economic evaluation from 2019 in France. We aim to describe the process and results of the economic evaluation of tisagenlecleucel and axicabtagene ciloleucel as well as the challenges these evaluations raised. Evaluations submitted by the firms were reviewed by HAS and submitted to the Committee of Economic Evaluation and Public Health (CEESP). The CEESP issued opinions related to: (1) the methodological quality of economic evidence and, (2) the cost-effectiveness and budget impact of the drugs. The CEESP invalidated the estimated incremental cost-utility ratios (ICUR) of tisagenlecleucel due to the insufficient clinical evidence and methodological quality to extrapolate the long-term progression of the disease after treatment and compare tisagenlecleucel with alternatives. The CEESP concluded that tisagenlecleucel was not proven cost-effective. The estimated ICUR of axicabtagene ciloleucel at €114,509/QALY vs. chemotherapies was associated with an acceptable level of methodological quality despite being based on a weak indirect comparison and limited data on quality of life. The CEESP considered axicabtagene ciloleucel ICUR to be "very high" and questioned the societal/community willingness-to-pay of the claimed price. The primary source of uncertainty surrounding the ICUR estimates of both drugs was the lack of hindsight on effectiveness. The economic evaluation of CAR-T cell therapies highlights the risk of inefficient resource allocation driven by limited clinical data. It calls for payment schemes accounting for this risk and effective collection of post-marketing data.

Bevacizumab in recurrent ovarian cancer.

PURPOSE: The cost-effectiveness of bevacizumab has been the subject of debate, and we aimed to present our own retrospective data on its effect on survival in recurrent epithelial ovarian cancer. METHODS: Patients with recurrent ovarian, tubal and primary peritoneal cancer between October 2007 and June 2018 were grouped according to the platinum-free interval. The progression-free and overall survivals of the patients who had received chemotherapy only and chemotherapy with bevacizumab were calculated. RESULTS: Eighty patients had received chemotherapy (CT) only, and 65 had received CT+BV. In platinum-sensitive recurrent epithelial ovarian cancer (PSREOC) patients, the median progression-free survival (PFS) months was 7 months (95% CI; 5.5-8.4) in the group who had received CT only and 13 months (95% CI; 5.8-20.1) in the group who had received CT+BV (p=0.001) and for CT+BV HR (Hazard Ratio):0.39 (95% CI; 0.24-0.64) (p=0.001). The median PFS of platinum-resistant recurrent epithelial ovarian cancer (PRREOC) patients who had received CT only was determined as 2 (95% CI; 1.4-2.5) and as 10 (95% CI; 6.8-13.1) months for patients who had received CT+BV (p=0.001), for patients who had received CT+BV HR: 0.31 (95% CI; 0.17-0.58) (p=0.001). In both PSREOC and PRREOC patients, there was no difference between CT + BV and CT group in terms of overall survival (p=0.978 and p=0.738, respectively). CONCLUSION: A significant effect of bevacizumab on the progression-free survival of both platinum-sensitive and platinum resistant recurrent ovarian cancers has been demonstrated; however, this effect failed to impact overall survival. Therefore, it could be recommended to use bevacizumab, considering the cost-effectiveness in undeveloped and developing countries.

Cost-effectiveness analysis of cemiplimab vs pembrolizumab for treatment of advanced cutaneous squamous cell carcinoma.

BACKGROUND: Most cutaneous squamous cell carcinomas (CSCCs) can be treated with surgical excision or radiation; however, approximately 1% of patients develop advanced disease. In 2018, the FDA approved cemiplimab-rwlc as the first programmed cell death-1 (PD-1) monoclonal antibody for the treatment of patients with metastatic CSCC or locally advanced CSCC who are not candidates for curative surgery or curative radiation. In June 2020, pembrolizumab, another PD-1 monoclonal antibody, was approved for the treatment of patients with recurrent or metastatic CSCC who are not candidates for curative surgery or radiation. We previously reported on the cost-effectiveness of cemiplimab vs historical standard of care for the treatment of advanced CSCC from a US perspective. OBJECTIVE: To estimate the cost-effectiveness of cemiplimab vs pembrolizumab for patients with advanced CSCC in the United States. METHODS: A "partitioned survival" framework was used to assess the cost-effectiveness of cemiplimab vs pembrolizumab. Clinical inputs were based on the most recent data cut of the phase 2 trials for cemiplimab (EMPOWER-CSCC-1; NCT02760498) and pembrolizumab (KEYNOTE-629). Progression-free survival and overall survival were extrapolated using parametric models until all patients had progressed or died. Health state utilities were derived from data collected in the EMPOWER-CSCC-1 trial. Costs included drug acquisition, drug administration, disease management, terminal care, and adverse events and were based on published 2020 US list prices. To assess model uncertainty, 1-way sensitivity and probabilistic sensitivity analyses (PSA) were conducted, alongside scenario analyses evaluating key modeling assumptions. RESULTS: In the base case, cemiplimab resulted in an incremental gain of 3.44 life-years (discounted) and incremental cost-effectiveness ratio (ICER) of $130,329 per quality-adjusted life-year (QALY) vs pembrolizumab. At a willingness-to-pay threshold of $150,000/QALY, PSA indicated a 71% probability that cemiplimab is cost-effective when compared with pembrolizumab. Scenario analysis resulted in ICERs ranging from $115,909 to $187,374. CONCLUSIONS: Findings suggest that cemiplimab is a cost-effective treatment for patients with advanced CSCC, compared with pembrolizumab. These results should be interpreted cautiously in the absence of head-to-head trials; however, in the absence of such data, these results can be used to inform health care decisions over resource allocation. DISCLOSURES: This study was supported by Regeneron Pharmaceuticals, Inc., and Sanofi. Paul, Cope, Keeping, Mojebi, and Ayers are employees of PRECISIONheor, which received funding to produce this work. Chen, Kuznik, and Xu are employees and stockholders of Regeneron Pharmaceuticals, Inc. Sasane is an employee and stockholder of Sanofi, Inc. Konidaris, Atsou, and Guyot are employees of Sanofi, Inc. The authors were responsible for all content and editorial decisions and received no honoraria related to the development of this publication.

Cost-effectiveness Analysis of Ado-trastuzumab Emtansine (T-DM1) for the Adjuvant Treatment of Patients With Residual Invasive HER2+ Early Breast Cancer in the United States.

OBJECTIVE: Ado-trastuzumab emtansine (T-DM1) was recently approved for patients with human epidermal growth factor receptor 2 positive (HER2+) early breast cancer (eBC) with residual invasive disease after neoadjuvant taxane and trastuzumab-based treatment. Cost-effectiveness analysis was conducted to compare T-DM1 versus trastuzumab in the United States. MATERIALS AND METHODS: A Markov cohort-based model tracked clinical and economic outcomes over a lifetime horizon from a US payer perspective. The model included 6 health states: invasive disease-free, nonmetastatic (locoregional) recurrence, remission, first-line and second-line metastatic BC and death. Model state transitions were based on statistical extrapolation of the head-to-head KATHERINE study and published sources. Dosing and treatment duration reflected prescribing information and trials. Costs (2019 US dollars) associated with pharmaceutical treatment (wholesale acquisition costs), health state specific care, adverse events, and end-of-life care were included. Health state utilities were obtained from KATHERINE and published literature. RESULTS: T-DM1 dominated trastuzumab, yielding lower lifetime costs (-$40,271), and higher life-years (2.980) and quality-adjusted life-years (2.336). Results were driven by patients receiving T-DM1 spending less time in more costly downstream health states, as these patients are less likely to experience a recurrence overall, despite having a higher likelihood of metastatic disease (distant recurrence) in the subset of patients who experience recurrence. Probabilistic sensitivity analysis indicated robust results, with 96.7% of 5000 stochastic simulations producing dominance for T-DM1. The most influential variables were related to treatment costs, off treatment utilities, and health state costs. Additional scenario analyses tested a range of model inputs and assumptions, and produced consistent results. CONCLUSION: Relative to trastuzumab, T-DM1 treatment for patients with HER2+ eBC who have residual invasive disease after neoadjuvant taxane and trastuzumab-based treatment is likely to reduce the overall financial burden of cancer, while simultaneously improving patient outcomes.

Nivolumab vs Pembrolizumab for Treatment of US Patients With Platinum-Refractory Recurrent or Metastatic Head and Neck Squamous Cell Carcinoma: A Network Meta-analysis and Cost-effectiveness Analysis.

Importance: Nivolumab and pembrolizumab are approved for treating platinum-refractory recurrent or metastatic head and neck squamous cell carcinoma (R/M HNSCC). Physicians and patients are uncertain which drug is preferable, rendering a cost-effectiveness comparison between them necessary. Objective: To evaluate the cost-effectiveness of nivolumab vs pembrolizumab in treating platinum-refractory R/M HNSCC. Design, Setting, and Participants: Both the network meta-analysis and cost-effectiveness analysis included patients from the CheckMate 141 and the KEYNOTE 040 phase 3 randomized clinical trials. The Checkmate 141 trial started on May 1, 2014, with the present analysis based on a September 2017 data cutoff. The KEYNOTE 040 trial started on November 17, 2014, with the present analysis based on a May 15, 2017, data cutoff. A bayesian network meta-analysis that included 856 patients was carried out, and a cost-effectiveness analysis that included 487 patients was conducted by developing a partitioned survival model, both between February and November 2020. The robustness of the model was assessed via 1-way, 2-way, and probabilistic sensitivity analyses; subgroup analyses were included; and scenario analyses were conducted to investigate the associations of dosage adjustment of nivolumab with cost-effectiveness. Main Outcomes and Measures: Life-years, quality-adjusted life-years (QALYs), overall costs, and incremental cost-effectiveness ratios (ICERs) were measured. Results: In the cost-effectiveness analysis that included 487 patients, for US health care payers, when nivolumab was administered based on patient weight (3 mg/kg biweekly), at a willingness-to-pay (WTP) threshold of $100 000 per QALY, the probability of nivolumab being cost-effective compared with pembrolizumab was 56%; at a WTP threshold of $150 000 per QALY, the probability was 62%. When nivolumab was administered at a fixed dose of 240 mg biweekly or 480 mg monthly, at a WTP threshold of $100 000 per QALY, the probability of nivolumab being cost-effective was 42% to 45%; at a WTP threshold of $150 000 per QALY, the probability was 52% to 55%. Conclusions and Relevance: Findings from this network meta-analysis and cost-effectiveness analysis suggest considering both WTP threshold and patient body weight when choosing between nivolumab and pembrolizumab for the treatment of patients with platinum-refractory R/M HNSCC. When the WTP threshold was $100 000 per QALY, for patients weighing less than 72 kg, nivolumab (3 mg/kg, biweekly) was considered cost-effective; otherwise, pembrolizumab was preferable. When the WTP threshold was $150 000 per QALY, nivolumab (3 mg/kg biweekly) was considered cost-effective for patients weighing less than 75 kg; otherwise, fixed-dose nivolumab (240 mg biweekly or 480 mg monthly) provided more cost savings.

A cost-utility analysis of avelumab for metastatic Merkel cell carcinoma in Taiwan.

BACKGROUND: Metastatic Merkel cell carcinoma (mMCC) has traditionally been managed with palliative chemotherapy regimens or best supportive care (BSC). Avelumab, a novel anti-programmed death-ligand 1 (PD-L1) human monoclonal antibody for mMCC treatment, is being studied in the pivotal JAVELIN Merkel 200 trial. AIM: Incorporating trial results, this analysis aimed to evaluate the cost-utility of avelumab in Taiwan. METHODS AND RESULTS: A de novo partitioned-survival model with three key health states related to survival (progression-free disease, progressed disease, and death) was applied in this study. The data of clinical efficacy, safety, and patient utilities were obtained from the JAVELIN Merkel 200 trial, literature review, and Taiwanese clinical expert opinion. Cost-utility analysis was performed, and results were presented as cost per quality-adjusted life year (QALY) gained. For treatment-naïve patients, the incremental cost-effectiveness ratios (ICERs) for avelumab vs BSC and avelumab vs chemotherapy were US$44885.06 and US$42993.06 per QALY gained, respectively. As to treatment-experienced mMCC patients, avelumab was associated with ICERs of US$27243.06 (vs BSC)/US$26557.43 (vs chemotherapy) per QALY gained. All ICERs remained consistently within the willingness-to-pay (WTP) threshold of US$53,333.33 per QALY gained. CONCLUSION: This study demonstrated avelumab to be a cost-effective treatment option for both treatment-experienced and treatment-naïve mMCC patients with very poor prognosis in Taiwan.

Cost-effectiveness and drug wastage of immunotherapeutic agents for hematologic malignancies: a systematic review.

Introduction: Novel immunotherapeutic agents (e.g. monoclonal antibodies, antibody-drug conjugates, bispecific T-cell engagers) as treatment options for hematologic malignancies continue to emerge. These agents have been used as the standard of care in specific disease states and are associated with high costs. Value assessment of these therapies is of critical importance for coverage and reimbursement decision-making.Areas covered: We identified 15 immunotherapeutic agents through the U.S. FDA approvals for hematologic malignancies until 2018 and systematically reviewed related cost-effectiveness studies. Additionally, we examined whether drug wastage was accounted for in these studies.Expert opinion: We reviewed 51 studies for 14 identified immunotherapeutic agents that met the inclusion criteria for this systematic review. Three studies were observational-based, one study was model-based and incorporated observational data. The remaining studies were model-based with the majority of the model parameters extracted from randomized control trials (RCTs). Among 43 model-based economic evaluations, 13 studies accounted for drug wastage. Most of the studies showed favorable incremental cost-effectiveness ratios of immunotherapeutic agents-containing regimens when compared with no immunotherapeutic agents-containing regimens. Alemtuzumab, brentuximab vedotin, and daratumumab were not considered cost-effective across all the studies. Further investigations are warranted to establish the value of recent immunotherapeutic agents for hematologic malignancies.

The effectiveness and value of nadofaragene firadenovec, oportuzumab monatox, and pembrolizumab for BCG-unresponsive non-muscle-invasive bladder cancer.

DISCLOSURES: Funding for this summary was contributed by Arnold Ventures, California Health Care Foundation, The Donaghue Foundation, Harvard Pilgrim Health Care, and Kaiser Foundation Health Plan to the Institute for Clinical and Economic Review (ICER), an independent organization that evaluates the evidence on the value of health care interventions. ICER's annual policy summit is supported by dues from AbbVie, Aetna, America's Health Insurance Plans, Anthem, Alnylam, AstraZeneca, Biogen, Blue Shield of CA, Boehringer-Ingelheim, Cambia Health Services, CVS, Editas, Evolve Pharmacy, Express Scripts, Genentech/Roche, GlaxoSmithKline, Harvard Pilgrim, Health Care Service Corporation, HealthFirst, Health Partners, Humana, Johnson & Johnson (Janssen), Kaiser Permanente, LEO Pharma, Mallinckrodt, Merck, Novartis, National Pharmaceutical Council, Pfizer, Premera, Prime Therapeutics, Regeneron, Sanofi, Spark Therapeutics, uniQure, and United Healthcare. Beinfeld, McKenna, Rind, and Pearson are employed by ICER. Touchette received funding from ICER for work on this report and has also received fees from Monument Analytics and AstraZeneca, unrelated to this work. The University of Illinois at Chicago (UIC) and Touchette hold a patent for the model described in this report. The model is included in ICER's Interactive Modeler, for which a fee is paid to UIC and Touchette. Atlas also received funding from ICER for work on this report.