Cost-effectiveness of Trastuzumab Deruxtecan for HER2-low Advanced Breast Cancer in the United States.

PURPOSE: Trastuzumab deruxtecan has been shown to be effective for advanced breast cancer with low levels of human epidermal growth factor receptor 2. To optimize the allocation of limited health care resources, this study evaluated the cost-effectiveness of trastuzumab deruxtecan from the US payer perspective. METHODS: A partitioned survival model was developed to project the disease course of advanced breast cancer. Clinical efficacy, treatment utilization, safety, and cost data were gathered from the DESTINY-Breast04 (Trastuzumab Deruxtecan in Previously Treated HER2-Low Advanced Breast Cancer) trial and the Centers for Medicare & Medicaid Services. Transition probabilities were obtained from the reported survival probabilities per DESTINY-Breast04 group. The incremental cost-effectiveness ratio (ICER), the incremental monetary benefit, and the incremental net health benefit were measured. One-way sensitivity analysis, probabilistic sensitivity analysis, and subgroup analysis were performed to explore the uncertainty of the model. FINDINGS: Trastuzumab deruxtecan had an ICER of $307,751 per quality-adjusted life-year (QALY) gained, with an incremental net health benefit of -0.317 QALY and an incremental monetary benefit of -$63,313 compared with the physician's choice of alternative chemotherapy agents. Subgroup analysis indicated that trastuzumab deruxtecan had an ICER of $383,776 per QALY gained for the hormone receptor-positive subgroup and an ICER of $194,424 per QALY for the hormone receptor-negative subgroup. One-way sensitivity analysis showed that the cost of trastuzumab deruxtecan had the most impact on model outcomes. The cost-effectiveness acceptability curve projected that the probability of trastuzumab deruxtecan being cost-effective was 5% in the overall population, 2% in the hormone receptor-positive subgroup, and 56% in the hormone receptor-negative subgroup at the willingness-to-pay threshold of $200,000 per QALY. IMPLICATIONS: Trastuzumab deruxtecan may be a cost-effective option for hormone receptor-negative patients with advanced breast cancer with low levels of human epidermal growth factor receptor 2.

Estimated projection of incidence and mortality of alcohol-related liver disease in China from 2022 to 2040: a modeling study.

BACKGROUND: China has one of the highest numbers of liver disease cases in the world, including 6.4 million cirrhosis associated with alcohol-related liver disease (ALD) cases. However, there is still a lack of urgent awareness about the growth of alcohol consumption and the increased burden of ALD in China. Therefore, we aimed to project the potential impact of changes in alcohol consumption on the burden of ALD in China up to 2040 under different scenarios. METHODS: We developed a Markov model to simulate the natural history of ALD until 2040 in China. We estimated the incidence and mortality of alcohol-related cirrhosis and hepatocellular carcinoma between 2022 and 2040 under four projected scenarios: status quo scenario and scenarios with a 2%, 4%, and 8% annual decrease in excessive alcohol consumption, respectively. RESULTS: Under the status quo scenario, the cumulative new cases of cirrhosis from 2022 to 2040 was projected to be 3.61 million (95% UI 3.03-4.44 million), resulting in a cumulative 1.96 million (1.66-2.32 million) deaths from alcohol-related cirrhosis and hepatocellular carcinoma. However, a 2% annual reduction in excessive alcohol consumption was expected to avert 0.3 million deaths associated with ALD, and a 4% annual reduction was projected to prevent about 1.36 million new cases of cirrhosis and prevent 0.5 million ALD-related deaths. Moreover, an 8% annual reduction would prevent about 2 million new cases of cirrhosis and 0.82 million deaths. CONCLUSIONS: Without any substantial change in alcohol attitudes and policies to regulate excessive drinking, the disease burden of ALD in China will increase enormously. Strengthening the implementation of alcohol restriction interventions is critical and urgent to reduce the impact of ALD on the Chinese population.

First-line systemic treatment strategies for unresectable hepatocellular carcinoma: A cost-effectiveness analysis.

BACKGROUND: Oral multikinase inhibitors and immune checkpoint inhibitors (ICIs) are effective for treating advanced hepatocellular carcinoma (aHCC) but may increase cost. This study compared the cost-effectiveness of oral multikinase inhibitors and ICIs in the first-line treatment of patients with aHCC. METHODS: A three-state Markov model was established to study the cost-effectiveness of drug treatment from the perspective of Chinese payers. The key outcomes in this study were total cost, quality-adjusted life years (QALYs), and the incremental cost-effectiveness ratio (ICER). RESULTS: The total costs and QALYs of sorafenib, sunitinib, donafenib, lenvatinib, sorafenib plus erlotinib, linifanib, brivanib, sintilimab plus IBI305, and atezolizumab plus bevacizumab were $9070 and 0.25, $9362 and 0.78, $33,814 and 0.45, $49,120 and 0.83, $63,064 and 0.81, $74,814 and 0.82, $81,995 and 0.82, $74083 and 0.85, and $104,188 and 0.84, respectively. The drug regimen with the lowest ICER was sunitinib ($551 per QALY), followed by lenvatinib ($68,869 per QALY). For oral multikinase inhibitors, the ICER of lenvatinib, sorafenib plus erlotinib, linifanib and brivanib compared with sunitinib was $779576, $1534,347, $1768,971, and $1963,064, respectively. For ICIs, sintilimab plus IBI305 is more cost effective than atezolizumab plus bevacizumab. The model was most sensitive to the price of sorafenib, the utility of PD, and the price of second-line drugs. CONCLUSION: For oral multikinase inhibitors, the order of possible treatment options is sunitinib > lenvatinib > sorafenib plus erlotinib > linifanib > brivanib > donafenib. For ICIs, the order of possible treatment options is sintilimab plus IBI305 > atezolizumab plus bevacizumab.

Alpha emitter radium-223 in patients with metastatic castration-resistant prostate cancer: A cost-utility analysis.

Objective: To assess the cost effectiveness of radium-223 dichloride for patients with metastatic castration-resistant prostate cancer (mCRPC) in China. Materials and methods: A Markov model was developed to estimate the long-term health and economic outcomes of radium-223 plus best standard care (BSC) treatment and BSC only for bone mCRPC patients over a lifetime horizon. The patients and interventions were modeled according to the ALSYMPCA trial. Costs were collected from a Chinese health system perspective. Utility values were derived from the published literature. The base-case model results were quality-adjusted life year (QALY), total cost, and incremental cost-utility ratio (ICUR). Uncertainty analyses were performed to assess the robustness of our conclusions. Results: Compared with the BSC arm, radium-223 achieved an excess 0.344 QALYs with an incremental cost of $29,459, resulting in an ICUR of $85,647 per QALY. The probability of Ra-223 being cost effective for the patients with bone mCRPC was sharply low (<0.5%) at a willingness-to-pay threshold of $38,136/QALY. Uncertainty analyses revealed that the model is robust to all the input parameters. Conclusion: Radium-223 is unlikely to be cost effective in patients with bone mCRPC at the current WTP threshold, from a Chinese health system perspective. In affluent areas with a high per-capita GDP, radium-223 therapy may be cost effective.

Cost-effectiveness analysis of tislelizumab, nivolumab and docetaxel as second- and third-line for advanced or metastatic non-small cell lung cancer in China.

Objective: Domestic PD-1inhibitor tislelizumab has emerged as a promising treatment for Chinese patients with driver-negative advanced or metastatic non-small cell lung cancer (NSCLC). The purpose of our study to evaluate whether tislelizumab is cost-effective as a second- or third-line treatment for this population compared with docetaxel (conventional chemotherapy) and nivolumab (imported PD-1inhibitor), from the perspective of the Chinese healthcare system. Material and Methods: A Markov model with a 3-week Markov cycle and a 30-year time horizon was built to compare the cost-effectiveness of second- or third-line tislelizumab versus docetaxel and nivolumab. Transition probabilities, including disease progression, survival, and adverse events (AEs)-related treatment discontinuation event, were estimated from the clinical trials. Costs and health utilities were collected from local hospitals, public database and published literature. Results: Compared with docetaxel, tislelizumab provided an additional 0.33 quality-adjusted life-years (QALYs) (1.37 vs. 1.04 QALYs) at an incremental cost of $9,286 ($23,646 vs. $14,360) for Chinese patients with driver-negative advanced or metastatic NSCLC, resulting in an incremental cost-effectiveness ratio (ICER) of $27,959/QALY under the WTP threshold of $35,663/QALY used in the model. Compared with nivolumab, tislelizumab was associated with a lower cost ($23,646 vs. $59,447) and higher QALYs (1.37 vs. 1.20 QALYs), resulting in its dominance of nivolumab. Conclusion: From the perspective of the Chinese healthcare system, domestic PD-1inhibitor tislelizumab immunotherapy represents a cost-effective treatment strategy compared with conventional docetaxel chemotherapy and imported PD-1inhibitor nivolumab immunotherapy in the treatment of driver-negative advanced or metastatic NSCLC beyond the first-line setting. In the era of "Universal Medical Insurance System", the rational use of domestic anticancer drugs guided by cost-benefit evidence would be an effective means to balance the limited expenditure of medical insurance fund and the growing demand for cancer treatments.

Benefit-to-harm ratio and cost-effectiveness of government-recommended gastric cancer screening in China: A modeling study.

Objective: Current guidelines recommend the gastric cancer risk score scale (GCRSS) for screening in gastric cancer (GC) high-risk populations in China. This study aimed to estimate the clinical benefits, harms, cost, and cost-effectiveness of the GCRSS screening strategy from a Chinese healthcare system perspective. Materials and methods: Using a microsimulation model, we evaluated 7 screening scenarios of the GCRSS with varying starting ages. We simulated 100,000 individuals from the age of 20 for each screening scenario. The main outcomes included GC incidence reduction, number of cause-specific deaths, costs, quality-adjusted life year (QALY), incremental cost-effectiveness ratio (ICER), and benefit-to-harm ratio. Deterministic and probabilistic sensitivity analyses were done to explore the robustness of model findings. Results: Screening with the GCRSS strategy at the age of 40 years (40-GCRSS) provided the greatest reduction of GC incidence by 70.6%, with 7,374 GC deaths averted per 100,000 individuals and the lowest benefit-to-harm ratio of 0.392. Compared with no screening or previous less costly strategy, at a willingness-to-pay (WTP) threshold of $37,655 per QALY, the 40-GCRSS strategy was cost-effective, with ICERs of $12,586 and $29,115 per QALY, respectively. Results were robust across univariate and probabilistic sensitivity analyses. The 40-GCRSS strategy showed a 0.856 probability of being cost-effective at a $37,655 per QALY WTP threshold. Conclusions: The findings suggest that the GCRSS strategy is effective and cost-effective in reducing the GC disease burden in China from a Chinese healthcare system perspective. Screening from the age of 40 would be the optimal strategy.

Cost-Effectiveness Analysis of Trastuzumab Deruxtecan versus Trastuzumab Emtansine in Human Epidermal Growth Factor Receptor 2-Positive Metastatic Breast Cancer in the USA.

INTRODUCTION: Based on data from the DESTINY-Breast03 trial, we performed a cost-effectiveness analysis of trastuzumab deruxtecan (T-DXd) in patients with human epidermal growth factor receptor 2 (HER2)-positive metastatic breast cancer who had been previously treated with trastuzumab and a taxane from the US payer perspective. METHODS: We conducted a Markov model to assess the cost-effectiveness of T-DXd versus trastuzumab emtansine (T-DM1). The simulation time horizon for this model was the lifetime of patients. Transition probabilities were based on data from the DESTINY-Breast03 trial. Health utility data were derived from published studies. Outcome measures were costs (in 2022 US$), quality-adjusted life-years (QALYs), and the incremental cost-effectiveness ratio (ICER). One-way and probabilistic sensitivity analyses assessed the uncertainty of key model parameters and their joint impact on the base-case results. RESULTS: The base-case results found that T-DXd provided an improvement of 3.90 QALYs compared with T-DM1, and the ICER was $220,533 per QALY. The one-way sensitivity analysis demonstrated that the utility value of progression-free survival, hazard ratios of T-Dxd versus T-DM1, and cost of T-Dxd contributed substantial uncertainty to the model. Probabilistic sensitivity analysis predicted T-DXd being cost-effective compared to T-DM1 was 0, 1, 16, and 46% at willingness-to-pay of $50,000, $100,000, $150,000, and 200,000 per QALY, respectively. CONCLUSION: T-DXd was unlikely to offer a reasonable value for the money spent compared to T-DM1 in a US payer setting.

Cost-Effectiveness of Pembrolizumab Plus Chemotherapy as First-Line Therapy for Advanced Oesophageal Cancer.

Objective: Pembrolizumab plus chemotherapy is recommended as the first-line treatment for advanced oesophageal cancer. The objective of this study is to evaluate the cost-effectiveness of pembrolizumab plus chemotherapy as first-line therapy for advanced oesophageal cancer from the healthcare system perspective in China. Methods: Based on the KEYNOTE-590 trial, a Markov model was constructed to estimate the cost and effectiveness of pembrolizumab plus chemotherapy and placebo plus chemotherapy, respectively. Total costs, life years (LYs), quality-adjusted life years (QALYs), and incremental cost-effectiveness ratios (ICERs) were calculated. One-way, probabilistic sensitivity analyses (PSA), and subgroup analyses were adapted to test the model robustness. Result: Compared with the placebo group, pembrolizumab group obtained an additional 1.05 QALY, but the cost was also increased by $121,478.76. The ICER was $115,391.84 per QALY gained, which was higher than the willingness-to-pay (WTP) of $31,304.31. The results of One-way sensitivity analyses showed that the ICER was sensitive to the hazard ratio of PFS and per cycle cost of pembrolizumab. At a WTP threshold of $31,304.31, the probability of pembrolizumab plus chemotherapy being cost-effective was 0%. Conclusion: From the perspective of China healthcare system, pembrolizumab plus chemotherapy as first-line treatment is not cost-effective for patients with advanced oesophageal cancer compared with placebo plus chemotherapy.

Clinical Benefit and Cost Effectiveness of Risk-Stratified Gastric Cancer Screening Strategies in China: A Modeling Study.

BACKGROUND AND OBJECTIVE: A new gastric cancer screening scoring system (NGCS) strategy was recommended for the early gastric cancer (GC) screening process in China. The current study aimed to assess the clinical benefits and the cost effectiveness of the NGCS strategy in GC high-risk areas of China from a societal perspective. METHODS: A Markov microsimulation model was developed to evaluate 30 alternative screening strategies with varying initiation age, including the NGCS strategy, the modified NGCS strategy, and the endoscopic screening strategy with various screening intervals. The primary outcomes included GC mortality, number of endoscopies, quality-adjusted life-years (QALYs), costs, and incremental cost-effectiveness ratios (ICERs). Cost estimates were reported in 2021 USD (US$) and both costs and benefits were discounted at 5% annually. Deterministic and probabilistic sensitivity analyses were performed to evaluate model uncertainty. RESULTS: Screening with the NGCS strategy from age 40 years (40-NGCS) reduced the GC incidence by 86.4%, which provided the greatest benefit across strategies. Compared with all strategies, at a willingness-to pay threshold of US$17,922 per QALY, the 40-NGCS strategy was a leading cost-effective strategy, with an ICER of US$15,668 per QALY. Results were robust in univariate and probabilistic sensitivity analyses. The probability of the 40-NGCS strategy being cost effective was 0.863. CONCLUSIONS: The 40-NGCS strategy was an effective and cost-effective strategy to reduce GC incidence and mortality in China. The findings provide important evidence for decision makers to formulate and optimize targeted approaches for GC prevention and control policies in China.

Cost-Effectiveness of Bevacizumab Biosimilar LY01008 Combined With Chemotherapy as First-Line Treatment for Chinese Patients With Advanced or Recurrent Nonsquamous Non-Small Cell Lung Cancer.

Objective: To investigate whether LY01008, a locally developed bevacizumab biosimilar agent, is appropriate for widespread use among Chinese advanced or recurrent nonsquamous non-small cell lung cancer (NSCLC) patients, our current study was designed to evaluate the cost-effectiveness of first-line LY01008 combined with platinum-doublet chemotherapy versus chemotherapy alone from the perspective of the Chinese healthcare system. Material and Methods: This economic evaluation designed a Markov model to compare the healthcare cost and quality-adjusted life-year (QALY) of first-line LY01008 combined with chemotherapy versus first-line chemotherapy. Transition probabilities, including disease progression, survival, and adverse event (AE)-related discontinuation of first-line treatment, were estimated using data from the clinical trials. Costs and health utilities were derived from local databases, hospitals, and published literature. Our base case analysis and scenario analysis focused on the cost-effectiveness of chemotherapy combined with a clinical trial dosage (15 mg/kg every 3-week cycle) and a real-world dosage (7.5 mg/kg every 3-week cycle) of LY01008, respectively. Results: In the base case analysis, first-line LY01008 combined with chemotherapy was associated with an increase of 0.48 QALYs in effectiveness and an increase of CNY 189,988 (US$ 26,240) in healthcare costs compared with first-line chemotherapy, resulting an incremental cost-effectiveness ratio (ICER) of CNY 375,425 (US$ 54,430)/QALY. In the scenario analysis, first-line LY01008 combined with chemotherapy was associated with a mean healthcare cost of CNY 265,060 (US$ 38,429), resulting an ICER of CNY 221,579 (US$ 32,125/QALY) between first-line LY01008 combined with chemotherapy versus first-line chemotherapy. The parameters that determine the cost of LY01008 have the greatest impact on the cost-effectiveness results. Conclusion: From the perspective of the Chinese healthcare system, first-line LY01008 at a real-world dosage combined with chemotherapy is likely to represent a cost-effective strategy compared with first-line chemotherapy alone for Chinese advanced or recurrent nonsquamous NSCLC patients.

Cost-Effectiveness Analysis of Hepatic Arterial Infusion Chemotherapy of Infusional Fluorouracil, Leucovorin, and Oxaliplatin Versus Transarterial Chemoembolization in Patients With Large Unresectable Hepatocellular Carcinoma.

Purpose: The purpose of this study was to evaluate a cost-effectiveness analysis of hepatic arterial infusion chemotherapy with infusional fluorouracil, leucovorin, and oxaliplatin (FOLFOX-HAIC) as the first-line treatment for patients with large unresectable hepatocellular carcinoma (HCC) compared with transarterial chemoembolization (TACE). Methods: A Markov model was constructed to simulate the first-line treatment, disease recurrence, and survival of patients with large unresectable HCC. Transition probabilities were based on clinical trial data. The costs and health utilities were derived from the public literature. The outputs were total cost, quality-adjusted life year (QALY), and incremental cost-effectiveness ratios (ICER). One-way and probabilistic sensitivity analyses were performed to examine model uncertainty. We also performed subgroup analyses. Results: The results of the base case analysis found that FOLFOX-HAIC increased overall costs by $9,381 and improved effectiveness by 1.01 QALYs compared with TACE. The one-way sensitivity analysis showed that the hazard ratio of progression-free survival and overall survival for FOLFOX-HAIC relative to TACE had the greatest impact on the ICER. Probabilistic sensitivity analysis found that the probability of FOLFOX-HAIC treatment being cost-effective was 99.54% at the willingness-to-pay threshold of $30,552/QALY. Patients in most subgroups favored FOLFOX-HAIC treatment because it had a more than 50% probability of being cost-effective than TACE, except for patients with negative hepatitis B infection. Conclusion: In conclusion, our study found that the FOLFOX-HAIC was a cost-effective option compared to TACE for patients with large unresectable HCC in China.

Sintilimab Plus Bevacizumab Biosimilar Versus Sorafenib as First-Line Treatment for Unresectable Hepatocellular Carcinoma: A Cost-Effectiveness Analysis.

Objective: The ORIENT-32 clinical trial revealed that sintilimab plus bevacizumab biosimilar significantly improved the median progression-free survival and median overall survival (OS) compared with sorafenib. This analysis evaluated the cost-effectiveness of sintilimab plus bevacizumab biosimilar as a first-line treatment for unresectable hepatocellular carcinoma from the Chinese perspective of healthcare system. Materials and methods: A Markov model with three mutual health states was constructed to evaluate the economic outcome of sintilimab plus bevacizumab biosimilar. The model cycle was 21 days, and the simulation time horizon was a lifetime. The output parameters of the model were the total cost, life-year (LY), quality-adjusted LY (QALY), and incremental cost-effectiveness ratio (ICER). Sensitivity analyses were conducted to assess the robustness of the results. Results: The base-case results found that sintilimab plus bevacizumab biosimilar provided an improvement of 1.27 QALYs and 1.84 LYs compared with sorafenib, and the ICER was $23,352/QALY. The hazard ratio for OS had the greatest influence on the ICER. The probability of sintilimab plus bevacizumab biosimilar was 85% at willingness-to-pay thresholds of $30,552/QALY. Conclusion: The findings of this analysis suggested that sintilimab plus bevacizumab biosimilar was a cost-effective first-line therapy for patients with unresectable hepatocellular carcinoma.

Cost-Effectiveness of Ipilimumab Plus Anti-PD-1 Therapy Versus Ipilimumab Alone in Patients With Metastatic Melanoma Resistant to Anti-PD-(L)1 Monotherapy.

OBJECTIVE: The use of ipilimumab plus anti-PD-1 has recently been shown to significantly improve the survival of patients with metastatic melanoma resistant to anti-PD-(L)1 monotherapy. The study assessed the cost-effectiveness of ipilimumab plus anti-PD-1 therapy in this population from the US payer perspective. MATERIALS AND METHODS: A Markov model was created based on a retrospective analysis of patients with metastatic melanoma who were resistant to anti-PD-(L)1. Cost information was obtained from the Centers for Medicare and Medicaid Services and literature-based costs. The utility value was derived from the published literature. The results of the model was the total cost, quality-adjusted life-year (QALY), and incremental cost-effectiveness ratio (ICER). The uncertainty of the model was addressed through sensitivity analysis. In addition, we also conducted subgroup analysis. RESULTS: Ipilimumab plus anti-PD-1 provided an improvement of 1.39 QALYs and 2.48 LYs, at a ICER of $73,163 per QALY. The HR of OS was the variable that had the greatest impact on ICER. Compared to ipilimumab, the probability of ipilimumab plus anti-PD-1 being cost-effective was 94% at the WTP of $150,000/QALY. The results of the subgroup analysis showed that the ICER in the majority of the subgroups was less than $150,000/QALY. CONCLUSIONS: Ipilimumab plus anti-PD-1 was likely to be cost-effective compared to ipilimumab for patients with metastatic melanoma who are resistant to anti-PD-(L)1 at a WTP threshold of 150,000/QALY.

PD-L1 Test-Based Strategy With Nivolumab as the Second-Line Treatment in Advanced NSCLC： A Cost-Effectiveness Analysis in China.

OBJECTIVE: Our previous economic assessment found that nivolumab was not cost-effective for Chinese patients with advanced non-small cell lung cancer (NSCLC) and without EGFR mutations or ALK translocations, when compared with the standard second-line drug docetaxel. However, a greater survival benefit with nivolumab was observed for patients with 1% or greater tumor programmed death ligand 1 (PD-L1) expression. In view of this, we designed the present analysis to explore whether it is cost-effective to use the PD-L1 test to guide second-line nivolumab treatment in China. MATERIAL AND METHODS: A Markov model was established to project the lifetime costs and quality-adjusted life-years (QALYs) of three second-line treatment strategies: nivolumab and docetaxel (strategies without a PD-L1 test) and PD-L1 test-based strategy. Deterministic and probabilistic sensitivity analyses were performed to examine the robustness of our results. Additional price reduction and willingness-to-pay (WTP) threshold scenario analyses were performed to explore the impact of economic and health policies with Chinese characteristics on our results. RESULTS: The PD-L1 test-based strategy costs approximately CNY 194,607 (USD 28,210) or more and yielded an additional 0.27 QALYs compared to the docetaxel strategy without a PD-L1 test, equating an incremental cost-effectiveness ratio (ICER) of CNY 731,089 (USD 105,978)/QALY. Deterministic sensitivity analyses showed that the price of nivolumab was the strongest source of variation in the ICERs. Probability sensitivity analysis showed that the probability for the PD-L1 test-based strategy being cost-effective increases with the increase of WTP thresholds. CONCLUSION: From the perspective of the Chinese healthcare system, using a PD-L1 test to guide second-line nivolumab treatment was not cost-effective. The National Healthcare Security Administration negotiation on the price reduction of nivolumab was found to be the most effective action to improve its cost-effectiveness in China.

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.

Cost-Effectiveness of Domestic PD-1 Inhibitor Camrelizumab Combined With Chemotherapy in the First-Line Treatment of Advanced Nonsquamous Non-Small-Cell Lung Cancer in China.

Objective: Camrelizumab is the first domestic PD-1inhibitor approved to be combined with chemotherapy as a first-line therapy for advanced nonsquamous non-small-cell lung cancer (NSCLC) in China. The purpose of this study was to determine whether using camrelizumab in the first-line setting is cost-effective in China when compared with traditional chemotherapy or the imported PD-1inhibitor pembrolizumab. Material and Methods: A Markov model was built to simulate 3-week patient transitions over a 30-year horizon from the perspective of the Chinese healthcare system. Health states included stable disease, first progression, second progression, and death. A direct comparison between first-line camrelizumab in combination with pemetrexed and carboplatin (CPC) and pemetrexed plus carboplatin (PC) was performed by calculating transition probabilities from the CameL trial. An indirect comparison between first-line CPC and pembrolizumab in combination with pemetrexed and platinum (PPP) was performed by calculating transition probabilities using a network meta-analysis. Costs in the Chinese setting were collected from the local public database and literatures. Sensitivity analyses explored the uncertainty around model parameters. Results: In the primary analysis, first-line CPC gained an additional 0.41 quality-adjusted life-years (QALYs) with an incremental cost of $3,486 compared with PC, resulting in an incremental cost-effectiveness ratio (ICER) of $8,378 per QALY gained. In the secondary analysis, first-line PPP yielded an additional 0.10 QALYs at an incremental cost of $6,710, resulting in an ICER of $65,563 per QALY gained. Conclusion: For Chinese patients with advanced nonsquamous NSCLC without targetable genetic aberrations, our primary analysis results supported first-line CPC as a cost-effective treatment compared with traditional PC chemotherapy. The findings of our secondary analysis suggested that first-line PPP would not be a cost-effective option compared with first-line CPC. This analysis provided strong evidence for promoting the widespread use of first-line CPC in China and, to some extent, stimulated the enthusiasm for the development of domestic cancer drugs.

Cost-Effectiveness of Avelumab Maintenance Therapy for Advanced or Metastatic Urothelial Carcinoma in the United States.

INTRODUCTION: The JAVELIN Bladder 100 trial showed that maintenance avelumab therapy after chemotherapy improved the survival of patients with advanced or metastatic urothelial carcinoma. We analyzed the cost-effectiveness of maintenance therapy with avelumab plus best supportive care (BSC) in patients with advanced or metastatic urothelial carcinoma after receiving first-line platinum-based chemotherapy from the US payer perspective. METHODS: A Markov model was used to analyze the economic outcomes of maintenance avelumab plus BSC (avelumab strategy) in the treatment of urothelial carcinoma. The clinical data were derived from the JAVELIN Bladder 100 trial. All cost information was obtained from Medicare and published literature. The total cost, total life years (LYs), total quality-adjusted LYs (QALYs), incremental cost-effectiveness ratio (ICER), and incremental net health benefit (INHB) were calculated. One-way sensitivity analysis and probabilistic sensitivity analysis were also performed. RESULTS: Our results showed that avelumab strategy versus BSC strategy cost US $176,352 and $238,661 and yielded an additional 0.465 and 1.007 QALY in all patients with unknown programmed-death ligand 1 (PD-L1) status and the PD-L1-positive subpopulation, respectively, which led to an ICER of $102,365/QALY and $106,253/QALY gained. In all patients with unknown PD-L1 status, maintenance avelumab plus BSC therapy guiding by PD-L1 expression testing (PD-L1-guided strategy) compared with the avelumab strategy and BSC strategy resulted in ICER of $105,360/QALY and $122,653/QALY, respectively. The probabilities of the avelumab strategy and the PD-L1-guided strategy being cost-effective in the simultaneous competition of the three strategies were 38.49% and 48.82%. In patients with PD-L1-positive status, the avelumab strategy had an 87.51% probability of cost-effectiveness. The most influential parameter for the model was the cost of avelumab and pembrolizumab. CONCLUSIONS: This analysis demonstrated that maintenance therapy with avelumab plus BSC may be a cost-effective option for patients with advanced or metastatic urothelial carcinoma at a willingness-to-pay (WTP) threshold of $150,000/QALY, especially for patients with PD-L1-positive status.

Cost-Effectiveness Analysis of Nivolumab Plus Ipilimumab for Advanced Non-Small-Cell Lung Cancer.

Objective: This study evaluated the cost-effectiveness of nivolumab plus ipilimumab vs. chemotherapy in the first-line setting for patients with advanced non-small-cell lung cancer (NSCLC) from the US payer perspective. Materials and methods: A Markov model wasdeveloped to evaluate the cost and effectiveness of nivolumab plus ipilimumab vs. chemotherapy in the first-line treatment of advanced NSCLC. The survival benefits of nivolumab plus ipilimumab were based on the results of the CheckMate 227 trial. The main endpoints of the model were cost, life-years (LYs), quality-adjusted LYs (QALYs), and incremental cost-effectiveness ratio (ICER). Univariable and probabilistic sensitivity analyses were conducted to assess model uncertainty. Additonal subgroup analyses were also performed. Results: nivolumab plus ipilimumab produced a gain of 0.62 QALYs, at a cost of $104238 per QALY. The variables that had the greatest influence on the ICER were body weight and overall survival (OS) hazard ratio (HR). The probability of nivolumab plus ipilimumab being cost-effectiveness compared to chemotherapy is 50.7 and 66.2% when the willingness-to-pay (WTP) value is $ 100,000 and $ 150,000 per QALY. The results of subgroup analyses showed the ICER remained below $150,000/QALY regardless of the PD-L1 expression level. Conclusions: nivolumab plus ipilimumab was estimated to be cost-effective compared with chemotherapy for patients with advanced NSCLC at a WTP threshold from 100,000/QALY to 150,000/QALY.

First-Line Chemo-Immunotherapy for Extensive-Stage Small-Cell Lung Cancer: A United States-Based Cost-Effectiveness Analysis.

OBJECTIVE: This study aimed to assess the cost-effectiveness of two recently approved first-line chemo-immunotherapies [atezolizumab combined with etoposide and platinum (AEP) and durvalumab combined with etoposide and platinum (DEP)] for patients with extensive-stage small-cell lung cancer (ES-SCLC) in the United States. MATERIAL AND METHODS: A Markov model was built to compare the cost and effectiveness of AEP, DEP, and etoposide plus platinum (EP) over a 10-year time horizon. Clinical efficacy and safety data were extracted from the IMpower 133 and CASPIAN trials. Health state utilities were obtained from published literature. Costs were collected from an US payer perspective. Deterministic and probabilistic sensitivity analyses were used to explore the uncertainty bound to model parameters. RESULTS: For the model cohort of adult patients with treatment-naive ES-SCLC, AEP was associated with marginal improved quality adjusted life years (QALYs) by 0.016 and reduced costs by $5,737 compared with DEP. When comparing the two chemo-immunotherapies with EP chemotherapy, AEP and DEP increased the QALYs by 0.162 QALYs and 0.146, respectively. However, both chemo-immunotherapies were associated with substantially health costs than EP, resulting in ICERs of $382,469 per QALY and $464,593 per QALY, respectively. CONCLUSION: In this cost-effectiveness study, first-line AEP represented a dominant treatment strategy compared with DEP. Despite neither first-line AEP nor first-line DEP was cost-effective compared with EP chemotherapy, AEP was able to provide a more efficient balance between incremental cost and QALY than DEP. When new combination therapies with remarkable effect become pivotal in the first-line treatment, the price reduction of these drugs may be essential to achieving cost-effectiveness.

Cost-Effectiveness Analysis of Cemiplimab Versus Chemotherapy as First-Line Treatment in Advanced NSCLC with PD-L1 Expression Levels of at Least 50.

INTRODUCTION: Cemiplimab may significantly increase overall survival in the first-line treatment of advanced non-small cell lung cancer (NSCLC) with a PD-L1 level of at least 50%. Therefore, there is a need to consider the cost-effectiveness of using this therapy for this indication. METHODS: This Markov model was built to estimate the cost and effectiveness of cemiplimab vs. chemotherapy in the first-line treatment of advanced NSCLC based on the data from the EMPOWER-Lung 1 trial. Life-years (LYs), quality-adjusted LYs (QALYs) and lifetime costs were estimated. One-way and probabilistic sensitivity analyses were performed to evaluate the model uncertainty. Additional subgroup analyses were performed. RESULTS: Treatment of advanced NSCLC with cemiplimab added 0.546 QALYs (1.492 LYs) and resulted in an incremental cost of $22,069.804 compared with chemotherapy, which was associated with an incremental cost-effectiveness ratio of $40,390.412 per QALY gained. The results of one-way sensitivity analysis found that the cost of cemiplimab was the most sensitive factor in our study. The probabilistic sensitivity analysis showed that the probability of cemiplimab being cost-effective was 100%. The subgroup analysis demonstrated that high PD-L1 expression (≥ 90%, > 60 to < 90% and ≥ 50 to ≤ 60%) also kept the incremental cost-effectiveness stable at $63,415.2450 per QALY, $61,896.446 per QALY and $-71,921.259 per QALY. CONCLUSION: From the perspective of US payers, cemiplimab is cost-effective in the first-line treatment of advanced NSCLC at the willingness-to-pay threshold of $150,000 per QALY.